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funding pulled
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This is a single centre non-randomised open label phase 1 trial of lung SBRT to part of a lung lesion in patients with advanced NSCLC in combination with pembrolizumab. This study will recruit up to 24 patients whose lung cancer has progressed beyond one line of palliative chemotherapy, and an EGFR or ALK inhibitor if an EGFR driver mutation or ALK gene rearrangement is present, respectively, and now requires further palliative systemic treatment.
The study will be conducted in two parts; an initial lung SBRT dose escalation phase (Part A), followed by a lung SBRT dose expansion cohort (Part B). The dose escalation phase is based on a 3+3 design such that patients will be treated in cohorts of 3-6 patients. A maximum of 12 patients will be allocated to one of two doses of lung SBRT in combination with pembrolizumab to determine the MTD, DLTs and RP2D. If there is more than one DLT in cohort 1, this treatment combination will be deemed as being unacceptable, and it would lead to termination of the study. Note, there is no de-escalation in cohort 1. During the dose expansion cohort, 12 patients will have lung SBRT dosed at the RP2D determined during the dose escalation phase in combination with pembrolizumab to obtain additional safety and response data. Maintenance pembrolizumab will continue until disease progression, unacceptable toxicities, the patient withdraws consent to the trial, or the patient has completed 24 months of treatment. A maximum of 24 patients will be treated in the study.
All patients will receive pembrolizumab on cycle (C) 1 day (D) 1, in Part A and B of the study. All patients will receive lung SBRT on C1D15, C1D17, and C1D19 as per lung SBRT protocol (See Appendix 3). Although C1D1 can occur +/- 3 days, C1D15, C1D17, and C1D19, must be scheduled for a Monday, Wednesday and Friday, respectively. Patients in part A will receive lung SBRT dosed at 30 Gy in 3# in cohort 1, or 54 Gy in 3# in cohort 2. Patients in Part B will receive the RP2D of lung SBRT, determined in Part A. All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks, until disease progression, unacceptable toxicities, the patient withdraws consent from the trial, or the patient has completed 24 months of treatment.
In the dose escalation phase, a minimum of 3 patients will be required per dose level being assessed. A minimum gap of 1 week will be left between the treatment of the first and the second, and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity. The DLT period for this study is 12 weeks from the last dose of lung SBRT (i.e. at C6D1). The dose escalation will be considered by the Safety Review Committee (SRC) once the 3rd or 6th patient in the cohort has completed the DLT period. If no DLT is observed at a dose level, then lung SBRT will be dose escalated to the next dosing level (see Table 1). If 1 out of 3 patients experience a DLT, then the cohort will be expanded to 6 patients. If 1 in 6 patients experience a DLT, then the dose will be escalated to the next dosing level. However, if ≥ 2 in 6 patients experience a DLT then the maximum administered dose (MAD) will have been reached, and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts. If the MAD is seen at dose level 1 then the study will be terminated. While waiting for 3 or 6 patients to complete the DLT period, no additional patients will be recruited. Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients.
Once the MTD has been determined the trial enters the dose expansion phase (unless the MTD is dose level 1). Here, 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab.
If there is ongoing clinical benefit at 24 months, the CI/PI will need to discuss with the sponsor and MSD, on a case by case basis for the continuation of pembrolizumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation cohort - DOSE LEVEL 1 | Other | Intervention: One dose pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. |
|
| Dose escalation cohort - DOSE LEVEL 2 | Other | Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. |
|
| Part B - Expansion cohort | Other | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) | Radiation | Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Dose Limiting Toxicity | Proportion of all treated patients who have experience at least one Dose Limiting Toxicity (DLT). DLT is assessed using NCI CTCAE v4.0 and defined as any one or more of: neutropenia with fever grade >=3; thrombocytopenia with bleeding grade >=3; any grade >=3 non-haematological toxicity which is definitely, probably, or possibly related to the trial treatment. | From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT |
| Measure | Description | Time Frame |
|---|---|---|
| Acute Toxicity Rate | Percentage of patients any acute toxicity, by worst grade as assessed using CTCAE v4.0 | From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT |
| Late Toxicity Rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fiona McDonald, MD | Royal Marsden NHS Foundation Trust | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Marsden NHS Foundation Trust | Sutton | Surrey | SM2 5PT | United Kingdom |
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During the period between June 2018 and January 2019, 2 patients were recruited to the study at the Royal Marsden Hospital in the United Kingdom.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation Cohort - DOSE LEVEL 1 | Intervention: One dose pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. Pembrolizumab administered as a 30-minute IV infusion. |
| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 14, 2017 |
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Dose Escalation phase with 2 dose levels followed by an Expansion phase
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| Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) | Radiation | Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 |
|
| Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose | Radiation | Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 |
|
| Pembrolizumab | Drug | Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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Percentage of patients with any late toxicity, by worst grade as assessed using CTCAE v4.0
| Assessed at start of each 21 day pembrolizumab cycle, starts from 12 weeks after last fraction of lung SBRT and ends 28 days after last on-trial dose of pembrolizumab (treatment ended at disease progression for all trial patients), up to 6 months |
| Overall Response Rate | Count of patients with best overall response of complete or partial response at any time, assessed using RECIST v1.1 | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients) |
| Disease Control Rate | Count of patients with best overall response at any time of complete or partial response, or stable disease, assessed by RECIST v1.1 | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients) |
| Overall Response Rate (irRECIST) | Count of patients with best response of complete or partial response, assessed using Immune Related Response Criteria (irRC) as defined by: Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune related response criteria. Clin Cancer Res 2009;15(23):7412. (72) | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression, start of new anti-cancer treatment, death or end of study |
| Frequency of PD-1/PD-L1 Expression | PD-1/PD-L1 expression distribution in responders and non-responders | Response to be defined as per previous endpoint, PD1/PD-L1 to be measured at study entry |
| Overall Survival at Six Months | Count of patients known to be alive at six months | 6 months after last dose of lung SBRT |
| Overall Survival at 12 Months | Count of patients known to be alive at 12 months | 12 months after last dose of lung SBRT |
| Progression Free Survival at 6 Months | Count of patients known to be alive and free from progression at 6 months | 6 months after last dose of lung SBRT |
| Progression Free Survival at 12 Months | Count of patients known to be alive and free from progression at 12 months | 12 months after last dose of lung SBRT |
| FG001 | Dose Escalation Cohort - DOSE LEVEL 2 | Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. Pembrolizumab administered as a 30-minute IV infusion. |
| FG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. Pembrolizumab administered as a 30-minute IV infusion. |
| COMPLETED |
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| NOT COMPLETED |
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No participants were recruited to Dose Level 2 of Dose Escalation Cohort and to Expansion Cohort.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation Cohort - DOSE LEVEL 1 | Intervention: One dose pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
| BG001 | Dose Escalation Cohort - DOSE LEVEL 2 | Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
| BG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
| BG003 | 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 (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) | Count of Participants | 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 | Proportion of Patients With Dose Limiting Toxicity | Proportion of all treated patients who have experience at least one Dose Limiting Toxicity (DLT). DLT is assessed using NCI CTCAE v4.0 and defined as any one or more of: neutropenia with fever grade >=3; thrombocytopenia with bleeding grade >=3; any grade >=3 non-haematological toxicity which is definitely, probably, or possibly related to the trial treatment. | All patients who completed the DLT period | Posted | Count of Participants | Participants | From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Acute Toxicity Rate | Percentage of patients any acute toxicity, by worst grade as assessed using CTCAE v4.0 | All patients who recieved at least one dose of trial treatment | Posted | Count of Participants | Participants | From first dose of Pembrolizumab to 12 weeks from the last dose of lung SBRT |
| ||||||||||||||||||||||||||||||||||
| Secondary | Late Toxicity Rate | Percentage of patients with any late toxicity, by worst grade as assessed using CTCAE v4.0 | All patients who received at least one dose of pembrolizumab and one fraction of radiotherapy | Posted | Count of Participants | Participants | Assessed at start of each 21 day pembrolizumab cycle, starts from 12 weeks after last fraction of lung SBRT and ends 28 days after last on-trial dose of pembrolizumab (treatment ended at disease progression for all trial patients), up to 6 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Overall Response Rate | Count of patients with best overall response of complete or partial response at any time, assessed using RECIST v1.1 | All patients with at least one dose of trial treatment | Posted | Count of Participants | Participants | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients) |
| ||||||||||||||||||||||||||||||||||
| Secondary | Disease Control Rate | Count of patients with best overall response at any time of complete or partial response, or stable disease, assessed by RECIST v1.1 | All patients with at least one dose of trial treatment | Posted | Count of Participants | Participants | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression (occurred no later than 7 months from start of treatment for all patients) |
| ||||||||||||||||||||||||||||||||||
| Secondary | Overall Response Rate (irRECIST) | Count of patients with best response of complete or partial response, assessed using Immune Related Response Criteria (irRC) as defined by: Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune related response criteria. Clin Cancer Res 2009;15(23):7412. (72) | No patients were assessed using irRECIST, as the study was terminated early after treating a total of two patients. Although imaging was performed and standard response measurement were done as per RECIST, the sum of the products of the two longest perpendicular diameters as required by irRECIST was not measured. | Posted | Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression, start of new anti-cancer treatment, death or end of study |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Frequency of PD-1/PD-L1 Expression | PD-1/PD-L1 expression distribution in responders and non-responders | The planned tissue evaluation for PD1/PD-L1 status was not done (and will not be performed in future) as the study was terminated early after treating a total of two patients | Posted | Response to be defined as per previous endpoint, PD1/PD-L1 to be measured at study entry |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival at Six Months | Count of patients known to be alive at six months | All patients assessed for survival at six months following last dose of lung SBRT | Posted | Count of Participants | Participants | 6 months after last dose of lung SBRT |
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| Secondary | Overall Survival at 12 Months | Count of patients known to be alive at 12 months | All patients assessed for survival at 12 months | Posted | Count of Participants | Participants | 12 months after last dose of lung SBRT |
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| Secondary | Progression Free Survival at 6 Months | Count of patients known to be alive and free from progression at 6 months | All patients assessed for progression and survival at 6 months | Posted | Count of Participants | Participants | 6 months after last dose of lung SBRT |
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| Secondary | Progression Free Survival at 12 Months | Count of patients known to be alive and free from progression at 12 months | All patients assessed for progression and survival at 12 months | Posted | Count of Participants | Participants | 12 months after last dose of lung SBRT |
|
Adverse events were recorded from confirmation of entry into the trial at the start of each 21 day pembrolizumab cycle, until the patients 30 day safety follow up visit. All cause mortality was recorded up to 12 months after last dose of lung SBRT.
No patients were recruited to Dose Level 2 of Dose Escalation Cohort and to Expansion Cohort, therefore number of patients at risk is 0 for these.
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| 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 Cohort - DOSE LEVEL 1 | Intervention: One dose pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 30 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG001 | Dose Escalation Cohort - DOSE LEVEL 2 | Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. | 0 | 0 | 0 | 0 | 0 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Bruising | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| PRIMING Senior Trial Manager | The Royal Marsden NHS Foundation Trust | (+44) 02089156666 | priming.trial@rmh.nhs.uk |
| Feb 9, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
Not provided
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| >=65 years |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
|
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
|
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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Intervention: One dose of pembrolizumab 200 mg (week 1) followed by lung Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#) in week 3. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) 54 Gy 3 fractions (#): Stereotactic Body Radiotherapy (SBRT) dosed at 54 Gy in 3 fractions (#) in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 |
| Part B - Expansion Cohort |
Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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| OG002 | Part B - Expansion Cohort | Intervention: One dose of pembrolizumab 200 mg (week 1) followed in by lung Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose determined in Part A in week 3, dosed at the maximum tolerated dose determined in Part A. Treatment with pembrolizumab 200 mg will be continued given every 3 weeks. Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose: Stereotactic Body Radiotherapy (SBRT) dosed at the maximum tolerated dose (MTD) determined in Part A in week 3 Pembrolizumab: Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks. |
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