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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000627-33 | EudraCT Number |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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The purpose of this study is to determine whether using two drugs together called vandetanib and selumetinib is effective in the treatment of cancer. The first part of this study will include patients with any solid tumour and the second part of this study will include only patients with non small cell lung cancer. The four main aims of this clinical study are to find out:
The purpose of this Phase I study is to establish a safety and toxicity profile of combining two study drugs; vandetanib, a VEGFR (Vascular Endothelial Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor) inhibitor, with selumetinib a MEK (Mitogen Activated Kinase) inhibitor.
This is the first time the drugs have been used together. These types of drugs have shown an effect in non small cell lung cancer (NSCLC).
The study is in two parts; the dose escalation phase and the expansion phase.
In the dose escalation phase, 42-50 patients will receive different doses of vandetanib and increasing doses of selumetinib to establish a safe dose to recommend for the next stage of the study. Patients with any solid tumour will be eligible.
In the expansion phase, up to 30 patients will receive the dose recommended in the previous phase. Only patients with NSCLC will be eligible for this part of the study.
The expansion phase will look at further evaluating the safety of the drug combination and the anti-tumour activity. Patients in this cohort will be requested to also consent to have additional imaging assessments and optional tumour biopsies.
Study treatment is administered orally; vandetanib tablets once daily and selumetinib capsules once daily (OD)/twice daily (BD). Cycle 1 is 42 days long. Subsequent cycles are 28 days in length. Patients will receive a total of 6 cycles of the combination treatment. If the patient has not progressed after six cycles, they may be treated for further cycles following approval from the sponsor.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation Phase Cohort 1 (Steady state dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Dose Escalation Phase Cohort 2 (Steady state dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Dose Escalation Phase Cohort 3 (Steady state dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Dose Escalation Phase Cohort 4 (Steady state dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Dose Escalation Phase Cohort 5a (Steady state dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Serious Adverse Events, Non-serious Adverse Events and Treatment Emergent Adverse Events. | Number of serious adverse events, non-serious adverse events and treatment emergent adverse events. | Safety data was collected from the date of written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib, an average (mean) of 164 days (approximately 5.4 months). |
| Number of Dose Limiting Toxicities (DLTs) Within Each Cohort. | Number of DLTs within each cohort. | DLTs occurring in the first Cycle (up to Day 42). |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation Cohorts Only: PK Parameter Maximum Observed Plasma Concentration of Vandetanib. | Maximum observed plasma concentration of vandetanib post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 24 hours post dose on Day 4. 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
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Inclusion Criteria:
(Dose escalation cohorts) Histologically or cytologically proven solid tumour for which no conventional therapy exists or is declined by the patient
(Expansion cohort only) Histologically or cytologically confirmed NSCLC patients only, for which no conventional therapy exists or is declined by the patient.
If only cytologically confirmed, baseline biopsy is mandatory for a patient to be eligible.
For NSCLC patients to be eligible for the expansion cohort they must have received:
(Expansion cohort only) Measurable disease according to RECIST criteria Version 1.1 in final version of the protocol
Life expectancy of at least 12 weeks
World Health Organisation (WHO) performance status of 0-1
Baseline LVEF > 50%
Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient goes on study.
Laboratory Test Value required
Haemoglobin (Hb) ≥ 9.0 g/dL
Absolute neutrophil count ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9 /L
Normal serum calcium (adjusted)* 2.15-2.55 mmol/L
Normal serum magnesium* 0.60-1.0 mmol/L
Normal serum potassium >4.0 mmol/L
Either: Serum bilirubin ≥1.5 x upper limit of normal (ULN) This does not apply to patients with Gilbert's disease.
Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is permissible
Either: Calculated creatinine clearance (using the Wright or C&G formula) > 50 mL/min
Or: Isotope clearance measurement** ≥ 50 mL/min (uncorrected)
INR or aPTT < 1.5 x ULN
*or normal range according to the local laboratory
** Isotope clearance result to be used to confirm eligibility if calculated C&G/Wright method results in GFR of = 50 mL/min.
*** Therapeutic INR values (2.0-3.0) are acceptable to confirm eligibility for patients who are taking concomitant warfarin.
18 years or over
Ability to swallow and retain oral medications.
Written (signed and dated) informed consent and be capable of co-operating with treatment, and follow-up
Exclusion Criteria:
Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for investigational medicinal products) before treatment.
Patients who have been withdrawn from treatment with agents that target EGFR because of unacceptable toxicity (prior treatment with these agents is allowed) and those patients who have had EGFR dose reductions by 50% or more.
Expansion cohort only: Prior treatment with any agent that targets MEK or VEGFR
Any prior exposure to RAS or RAF inhibitors
Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of the Investigator and the Centre for Drug Development (CDD) should not exclude the patient.
Symptomatic brain metastases (patients must be stable for >3 months post RT treatment) or spinal cord compression.
Patients with interstitial lung disease.
Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrollment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.
Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
Major surgery from which the patient has not yet recovered.
At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
Cardiac conditions as follows:
Clinically significant cardiovascular event within 3 months prior to entry to include:
History of arrhythmia which is symptomatic or requires treatment (CTCAE V4.02), symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
Uncontrolled hypertension (BP > 160/100 despite optimal therapy)
Prior or current cardiomyopathy
Atrial fibrillation with heart rate > 100 bpm
QTcB > or equal to 450 msec on screening ECG (Note: If a patient has a QTcB interval > or equal to 450 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]. The average QTcB from the three screening ECGs must be < 450 msec in order for the subject to be eligible for the study.)
History of congenital long QT syndrome
History of Torsade de Pointes (or any concurrent medication with a known risk of inducing Torsades de Pointes.)
Concomitant medications that are potent inducers of CYP3A4 function i.e. rifampicin, rifabutin, phenytoin, carbamazepine, Phenobarbital and St John"s Wort.
Any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial (e.g. evidence of severe or uncontrolled systemic disease or concurrent condition or that may affect ability to absorb oral agents).
Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years or more and are deemed at negligible risk for recurrence, are eligible for the trial.
If a participant plans to participate in another interventional clinical study, whilst taking part in this Phase I study. Participation in an observational study would be acceptable.
Ophthalmological conditions as follows:
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| Name | Affiliation | Role |
|---|---|---|
| Denis Talbot, Prof | Oxford University Hospitals NHS Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Churchill Hospital | Headington | Oxford | United Kingdom | |||
| Addenbrooke's Hospital |
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| Label | URL |
|---|---|
| Simple summary of trial results on Cancer Research UK Trial Database | View source |
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Trial participants were enrolled at three trial sites between 10 January 2012 and 19 September 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 26, 2018 | Jun 10, 2021 |
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Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
|
| Dose Escalation Phase Cohort 5b (Steady state dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Dose Escalation Phase Cohort 6 (Steady state dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Experimental | Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. |
|
| Expansion Phase (Steady state dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Experimental | Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase. |
|
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Vandetanib, Selumetinib | Drug | Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
| Dose Escalation Cohorts Only: PK Parameter Maximum Observed Plasma Concentration of Selumetinib. | Maximum observed plasma concentration of selumetinib post treatment with the combination of vandetanib and selumetinib. | 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
| Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-24 Hours) of Vandetanib. | Area under the plasma concentration time curve (0-24 hours) of vandetanib post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 24 hours post dose on Day 4. 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
| Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-12 Hours) of Selumetinib. | Area under the plasma concentration time curve (0-12 hours) of selumetinib post treatment with the combination of vandetanib and selumetinib. This was extrapolated from the sampling data up to 10 hours to allow comparison with literature data. | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 10 hours post dose on Days 15 and 29. |
| Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-12 Hours) of N-desmethyl Metabolite of Selumetinib. | Area under the plasma concentration time curve (0-12 hours) of N-desmethyl metabolite of selumetinib following the combination of vandetanib and selumetinib. This was extrapolated from the sampling data up to 10 hours to allow comparison with literature data. | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 10 hours post dose on Days 15 and 29. |
| Expansion Cohort Only: Progression Free Survival (PFS) of Patients With NSCLC After Treatment With the Combination of Vandetanib and Selumetinib. | PFS by Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0). Per RECIST for target lesions and assessed by computerised tomography (CT), progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum while on trial, or the appearance of one or more new lesions. | 10 and 18 weeks from date of first dose of vandetanib. |
| Expansion Cohort Only: One Year Survival of Patients With NSCLC After Treatment With the Combination of Vandetanib and Selumetinib. | Number of patients alive at one year. | 1 year from date of first dose of vandetanib. |
| Expansion Cohort Only: Tumour Metabolism in Patients With NSCLC Using Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) Criteria. | Tumour metabolism using 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) computerised tomography (CT) imaging pre and post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. These were assessed and reported according to PERCIST criteria. | Baseline, Day 12, Day 42. |
| Cambridge |
| United Kingdom |
| The Christie Hospital | Manchester | United Kingdom |
| Freeman Hospital | Newcastle | United Kingdom |
| FG001 | Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| FG007 | Dose Expansion Phase (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG001 | Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib ) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib ) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG007 | Expansion Phase (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| ||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Serious Adverse Events, Non-serious Adverse Events and Treatment Emergent Adverse Events. | Number of serious adverse events, non-serious adverse events and treatment emergent adverse events. | All patients who met the eligibility criteria and received at least one dose of the combination treatment (vandetanib and selumetinib) were evaluable for safety assessment (N=57). | Posted | Number | Adverse events | Safety data was collected from the date of written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib, an average (mean) of 164 days (approximately 5.4 months). |
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Dose Limiting Toxicities (DLTs) Within Each Cohort. | Number of DLTs within each cohort. | All patients who met the eligibility criteria and received at least one dose of the combination treatment (vandetanib and selumetinib) were evaluable for safety assessment (N=57). | Posted | Number | DLTs | DLTs occurring in the first Cycle (up to Day 42). |
| |||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Escalation Cohorts Only: PK Parameter Maximum Observed Plasma Concentration of Vandetanib. | Maximum observed plasma concentration of vandetanib post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. | All patients in the dose escalation cohorts (Cohorts 1 to 6) who received at least one dose of IMP (N=47 with available PK data). | Posted | Median | Full Range | ng/mL | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 24 hours post dose on Day 4. 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Escalation Cohorts Only: PK Parameter Maximum Observed Plasma Concentration of Selumetinib. | Maximum observed plasma concentration of selumetinib post treatment with the combination of vandetanib and selumetinib. | All patients in the dose escalation cohorts (Cohorts 1 to 6) who received at least one dose of IMP (N=47 with available PK data). | Posted | Median | Full Range | ng/mL | 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-24 Hours) of Vandetanib. | Area under the plasma concentration time curve (0-24 hours) of vandetanib post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. | All patients in the dose escalation cohorts (Cohorts 1 to 6) who received at least one dose of IMP (N=47 with available PK data). | Posted | Median | Full Range | h*ng/mL | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 24 hours post dose on Day 4. 0 hours (pre dose) and at 0.5, 2, 4, 6, 10 and 24 hours post dose on Days 15 and 29. |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-12 Hours) of Selumetinib. | Area under the plasma concentration time curve (0-12 hours) of selumetinib post treatment with the combination of vandetanib and selumetinib. This was extrapolated from the sampling data up to 10 hours to allow comparison with literature data. | All patients in the dose escalation cohorts (Cohorts 1 to 6) who received at least one dose of IMP (N=47 with available PK data). | Posted | Median | Full Range | h*ng/mL | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 10 hours post dose on Days 15 and 29. |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Dose Escalation Cohorts Only: PK Parameter Area Under the Plasma Concentration Time Curve (0-12 Hours) of N-desmethyl Metabolite of Selumetinib. | Area under the plasma concentration time curve (0-12 hours) of N-desmethyl metabolite of selumetinib following the combination of vandetanib and selumetinib. This was extrapolated from the sampling data up to 10 hours to allow comparison with literature data. | All patients in the dose escalation cohorts (Cohorts 1 to 6) who received at least one dose of IMP (N=47 with available PK data). | Posted | Median | Full Range | h*ng/mL | 0 hours (pre dose) and at 0.5, 2, 4, 6 and 10 hours post dose on Days 15 and 29. |
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Expansion Cohort Only: Progression Free Survival (PFS) of Patients With NSCLC After Treatment With the Combination of Vandetanib and Selumetinib. | PFS by Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0). Per RECIST for target lesions and assessed by computerised tomography (CT), progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum while on trial, or the appearance of one or more new lesions. | All patients in the expansion cohort receiving at least one cycle* of the vandetanib and selumetinib combination with a baseline assessment of disease (N=9). *To be evaluable for response, a patient must have received a minimum of 21 of the 28 daily doses of the combination treatment in Cycle 1. | Posted | Number | participants | 10 and 18 weeks from date of first dose of vandetanib. |
| |||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Expansion Cohort Only: One Year Survival of Patients With NSCLC After Treatment With the Combination of Vandetanib and Selumetinib. | Number of patients alive at one year. | All patients in the expansion cohort receiving at least one cycle* of the vandetanib and selumetinib combination with a baseline assessment of disease (N=9). *To be evaluable for response, a patient must have received a minimum of 21 of the 28 daily doses of the combination treatment in Cycle 1. | Posted | Number | participants | 1 year from date of first dose of vandetanib. |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Expansion Cohort Only: Tumour Metabolism in Patients With NSCLC Using Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) Criteria. | Tumour metabolism using 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) computerised tomography (CT) imaging pre and post treatment with vandetanib alone and following the combination of vandetanib and selumetinib. These were assessed and reported according to PERCIST criteria. | All patients in the expansion cohort receiving at least one cycle* of the vandetanib and selumetinib combination with a baseline assessment of disease (N=9). *To be evaluable for response, a patient must have received a minimum of 21 of the 28 daily doses of the combination treatment in Cycle 1. | Posted | Number | participants | Baseline, Day 12, Day 42. |
|
Safety data was collected from the date of written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib, an average (mean) of 164 days (approximately 5.4 months). Overall Mortality was collected during the Safety data assessment period for the dose Escalation Cohorts and up to one year after Cycle 1 Day 1 for the Expansion Cohort.
Per protocol, where deaths due to disease progression were reported as AEs, these weren't considered to be SAEs unless related to the IMP. These events were coded by the Sponsor as "Death NOS" in the clinical database but have been entered as disease progression at the request of ClinicalTrials.gov. For patients recruited to the expansion cohort, deaths due to disease progression in the survival follow-up period were not reported as AEs but have been included in the All-cause mortality numbers.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 0 | 6 | 4 | 6 | 6 | 6 |
| EG001 | Dose Escalation Phase Cohort 2 ( Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 1 | 6 | 4 | 6 | 6 | 6 |
| EG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 2 | 6 | 6 | 6 | 6 | 6 |
| EG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 0 | 7 | 2 | 7 | 7 | 7 |
| EG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 1 | 8 | 7 | 8 | 8 | 8 |
| EG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 0 | 7 | 5 | 7 | 7 | 7 |
| EG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 1 | 6 | 6 | 6 | 6 | 6 |
| EG007 | Expansion Phase (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. | 7 | 11 | 8 | 11 | 11 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac disorders - Other, specify | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Paroxysmal atrial tachycardia | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Eye disorders - Other, specify | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Retinal vascular disorder | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Retinopathy | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Obstruction gastric | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Disease Progression | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | CTCAE (4.02) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Stroke | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Ischemia cerebrovascular | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Urine discoloration | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Laryngeal hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Erythroderma | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (4.02) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Chest pain - cardiac | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Cardiac disorders - Other, specify | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hearing impaired | Ear and labyrinth disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Ear and labyrinth disorders - Other, specify | Ear and labyrinth disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Blurred vision | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Eye disorders - Other, specify | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Eyelid function disorder | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Flashing lights | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Floaters | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Glaucoma | Eye disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Bloating | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Esophageal hemorrhage | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Malabsorption | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Oral hemorrhage | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Stomach pain | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Chills | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Disease Progression | General disorders | CTCAE (4.02) | Systematic Assessment | Death due to disease progression (not considered related to IMP). Per protocol, cases of death due to disease progression were not considered to be SAEs, unless considered related to the IMP. |
|
| Edema limbs | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Flu like symptoms | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| General disorders and administration site conditions - Other, specify | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pain | General disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Allergic reaction | Immune system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Nail infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Papulopustular rash | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | CTCAE (4.02) | Systematic Assessment |
| |
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | CTCAE (4.02) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | CTCAE (4.02) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Cardiac troponin I increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Cholesterol high | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| CPK increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Investigations - Other, specify | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Weight loss | Investigations | CTCAE (4.02) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Buttock pain | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Muscle weakness upper limb | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.02) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Cognitive disturbance | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Extrapyramidal disorder | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Nervous system disorders - Other, specify | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Confusion | Psychiatric disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Libido increased | Psychiatric disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary frequency | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Urinary urgency | Renal and urinary disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Vaginal inflammation | Reproductive system and breast disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Nail loss | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Periorbital edema | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Photosensitivity | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Flushing | Vascular disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hot flashes | Vascular disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4.02) | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (4.02) | Systematic Assessment |
|
61 patients were enrolled. 3 withdrew before having vandetanib (Van) or selumetinib (Sel). 1 patient in Cohort 5b received Van but withdrew before having Sel and was excluded from the safety analysis. The remaining 57 patients had at least 1 dose of the combination and were included in the safety analysis population (46 in dose escalation, 11 in expansion). PFS was planned to be assessed at 12 weeks but was instead assessed at 10 and 18 weeks as disease assessments were performed every 2 cycles
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Regulatory Affairs Manager | Cancer Research UK Centre for Drug Development | +44 203 4696878 | regulatory@cancer.org.uk |
| Prot_000.pdf |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C452423 | vandetanib |
| C517975 | AZD 6244 |
Not provided
Not provided
Not provided
|
|
|
|
| Total NSAEs |
|
| Total treatment emergent AEs |
|
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG007 | Expansion Phase (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
|
Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long.
Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long.
Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
|
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
|
|
Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
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Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
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Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG002 | Dose Escalation Phase Cohort 3 (Steady State Dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG003 | Dose Escalation Phase Cohort 4 (Steady State Dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG004 | Dose Escalation Phase Cohort 5a (Steady State Dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG005 | Dose Escalation Phase Cohort 5b (Steady State Dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
| OG006 | Dose Escalation Phase Cohort 6 (Steady State Dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib) | Dose escalation to determine the recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib. Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment. |
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