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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000198-11 | EudraCT Number |
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| Name | Class |
|---|---|
| Quintiles, Inc. | INDUSTRY |
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This Phase 1, open label, single centre, non-randomised study in patients with advanced solid malignancies consists of two parts:
This is a Phase I, open label, single centre, non-randomised study in patients with advanced solid malignancies that is refractory or resistant to standard treatment or where no suitable effective standard treatment exists or for whom paclitaxel or fulvestrant are appropriate treatment choices. The study will be divided in two parts:
i. 50mg BD monotherapy ii. 125mg BD taken on first 2 days of treatment each week in combination with 500mg intramuscular fulvestrant on Day 1, Cycle 1, Day 15, Cycle 1; Day 1, Cycle 2, then Day 1 of each monthly cycle thereafter iii. 50mg BD taken on first 3 days of treatment each week for 6 weeks in combination with a single weekly paclitaxel infusion (80mg/m2 ) followed by a one week break from treatment where no AZD2014 or paclitaxel will be given. This 7 week schedule composes one cycle of treatment. Patients will be given up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.
Radiolabelled AZD2014 will be administered to fasted patients (i.e. no food 2 hours before and 1 hour after each dose). Non-radiolabelled AZD2014 will be administered either under fasted or non-fasted conditions. The safety and tolerability and anti-tumour activity of AZD2014 and combination with paclitaxel or fulvestrant will be evaluated in all enrolled patients respectively using conventional safety parameters, AEs/SAEs and RECIST 1.1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [14C]AZD2014 followed by AZD2014 Monotherapy | Experimental | Arm will be comprised of [14C]AZD2014 followed by AZD2014 Monotherapy |
|
| [14C]AZD2014 followed by AZD2014 + Fulvestrant | Experimental | Arm will be comprised of [14C]AZD2014 followed by AZD2014 + Fulvestrant |
|
| [14C]AZD2014 followed by AZD2014 + Paclitaxel | Experimental | Arm will be comprised of [14C]AZD2014 followed by AZD2014 + Paclitaxel |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]AZD2014 | Drug | Radiolabelled dual TORC1/TORC2 inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Total Radioactivity in Plasma Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period. |
| AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014 | The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
| AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014 | The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of AEs Experienced by Patients. | AEs (including serious AEs [SAEs]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented. | From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period. |
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Inclusion Criteria:
Exclusion Criteria:
Involvement in planning and/or conduct of the study
Previous enrolment in present study
Another study with an investigational product in last 28 days
Chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents & any investigational agents within 21 days of starting treatment (not including palliative radiotherapy at focal sites), or corticosteroids within 14 days
Major surgery within 4 weeks, or minor surgery within 14 days
Exposure to strong and moderate inhibitors or inducers of cytochrome P450 (CYP) 3A4/5, P-glycoprotein (Pgp) (multidrug resistance gene [MDR1]), and breast cancer resistance protein (BCRP), if taken within stated washout periods
Exposure to specific substrates of the drug organic anion-transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporting polypeptide (OCT)1 and OCT2 within appropriate washout period
Any haemopoietic growth factors (eg, filgrastim [granulocyte colony-stimulating factor; G-CSF], sargramostim [granulocyte-macrophage colony-stimulating factor; GM-CSF]) within 14 days prior to receiving study treatment
Previous treatment with AZD2014 or AZD8055
Patients who have received fulvestrant within 3 months
With exception of alopecia, any unresolved toxicities chemotherapy/radiotherapy should be no greater than CTCAE grade 1
Participated in another absorption, distribution, metabolism and excretion study within 1 year
Spinal cord compression and/or brain metastases unless asymptomatic or treated & stable off steroids for at least 4 weeks
Severe or uncontrolled systemic diseases (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, active bleeding diatheses or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
Recent history of drug abuse or alcohol abuse
Patients who have undergone any of the following procedures or experienced conditions currently or in preceding 12 months:
Abnormal echocardiogram at baseline (left ventricular ejection fraction [LVEF] <55% and shortening fraction [SF] <15%)
Torsades de Pointes either currently or within 12 months
Mean resting QTcF ≥470 ms
Medications known to prolong QT interval, or that increase the risk of QTc prolongation or arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of either long QT syndrome), or unexplained sudden death under 40 years of age
Laboratory values as listed below:
Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis
Abnormal fasting glucose >126 mg/dL (>7 mmol/L)
Patients with diabetes Type 1 or uncontrolled Type 2 (glycosylated haemoglobin [HbA1c] >8% [64 mmol/mol] assessed locally)
Current refractory nausea and vomiting, chronic gastrointestinal disease or inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption
History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014
Judgment that patient is unsuitable to participate in study and unlikely to comply with study procedures, restrictions & requirements
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| Name | Affiliation | Role |
|---|---|---|
| Emma Dean, MD | The Christie NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Manchester | M20 4BX | United Kingdom |
4 patients were enrolled (signed informed consent). Following [14C]-AZD2014, patients either continued AZD2014 as monotherapy or in combination with a standard regimen of fulvestrant or paclitaxel as appropriate and at the Investigator's discretion. No patients were recruited into AZD2014+paclitaxel treatment regimen.
First subject enrolled: 8 February 2016; Last Subject Last Visit: 21 December 2016 (End of Study [EoS]). The study was performed at a single study centre in the United Kingdom. Adult patients with advanced solid tumours refractory or resistant to standard therapies were recruited into this 2 period study.
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| ID | Title | Description |
|---|---|---|
| FG000 | [14C]-AZD2014 Then AZD2014 Monotherapy | Single Dose Period: Patients were given a single oral dose of radiolabelled AZD2014 ([14C]-AZD2014) as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to adverse events (AEs), withdrawal of consent, progression of disease according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. |
| FG001 | [14C]-AZD2014 Then AZD2014 + Fulvestrant | Single Dose Period: Patients were given a single oral dose of [14C]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Single Dose Period (Day 1 - 8) |
| |||||||||||||
| Multiple Dose Period (Day 8 - EoS) |
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All patients in the safety analysis set who received at least one dose of radiolabelled or non-radiolabelled AZD2014 were included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | [14C]-AZD2014 Then AZD2014 Monotherapy | Single Dose Period: Patients were given a single oral dose of [14C]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Total Radioactivity in Plasma Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | The Pharmacokinetic (PK) analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram equivalent/millilitre (ngEq/mL) | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period. |
|
TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
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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 | [14C]-AZD2014 Then AZD2014 Monotherapy | Single Dose Period: Patients were given a single oral dose of [14C]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic predose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Malaise | General disorders | MedDRA 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Candida infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
No patients were recruited into AZD2014 + paclitaxel treatment regimen, as per the protocol plan.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Science Director | AstraZeneca | clinicaltrialtransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| D000077267 | Fulvestrant |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 |
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| Multiple dose AZD2014 | Drug | Dual TORC1/TORC2 inhibitor |
|
| Fulvestrant | Drug | Hormonal Agent |
|
| Paclitaxel | Drug | Taxane |
|
| Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8 | The mean cumulative percentage of [14C]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | From pre-dose Day 1 to Day 8 of the Single Dose Period. |
| Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva | Mean AZD2014 Cmax values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva | AZD2014 Tmax values for plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva | AZD2014 t(last) values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Area Under the Plasma Concentration-time Curve (AUC) for AZD2014 | Mean AUC for AZD2014 following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva | Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Apparent Total Body Clearance (CL/F) of AZD2014 | The mean CL/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Mean Residence Time (MRT) of AZD2014 | The MRT of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma | The mean Vss/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma | The mean lambda_z of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma | The mean t1/2(lambda_z) for AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period. |
| Cmax for Total [14C] Radioactivity in Whole Blood and Saliva | Mean [14C] radioactivity Cmax values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Tmax for [14C] Radioactivity in Whole Blood and Saliva | [14C] radioactivity tmax in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 is presented . | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| T(Last) for [14C] Radioactivity in Whole Blood and Saliva | Mean [14C] radioactivity t(last) values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity | The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose. |
| Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva | The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R]) | Mean fe%(R) values per urine collection period are presented as a percentage of the total [14C]-AZD2014 dose administered on Day 1. | Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Renal Clearance (CL[R]) of AZD2014 From Plasma. | CL(R) of AZD2014 from plasma up to 168 h post-dose. | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R]) | fe cum%(R) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f]) | fe cum%(f) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
| Best Overall Response (BOR) Assessment | Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD). PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression. | RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period. |
| Best Percentage Change in Tumour Size From Baseline | Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions. | RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period. |
| NOT COMPLETED |
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| BG001 | [14C]-AZD2014 Then AZD2014 + Fulvestrant | Single Dose Period: Patients were given a single oral dose of [14C]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | [14C]-AZD2014 (Period 1 [Day 1 - 8]) | 125 mg [14C]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics. Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014. |
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| Primary | AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014 | The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ngEq/mL | Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014 | The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014 | The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ngEq/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8 | The mean cumulative percentage of [14C]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Mean | Standard Deviation | Percentage of dose administered | From pre-dose Day 1 to Day 8 of the Single Dose Period. |
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| Primary | Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva | Mean AZD2014 Cmax values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva | AZD2014 Tmax values for plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Median | Full Range | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva | AZD2014 t(last) values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Area Under the Plasma Concentration-time Curve (AUC) for AZD2014 | Mean AUC for AZD2014 following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva | Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Apparent Total Body Clearance (CL/F) of AZD2014 | The mean CL/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Mean Residence Time (MRT) of AZD2014 | The MRT of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma | The mean Vss/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma | The mean lambda_z of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma | The mean t1/2(lambda_z) for AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Cmax for Total [14C] Radioactivity in Whole Blood and Saliva | Mean [14C] radioactivity Cmax values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ngEq/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Tmax for [14C] Radioactivity in Whole Blood and Saliva | [14C] radioactivity tmax in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 is presented . | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Median | Full Range | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | T(Last) for [14C] Radioactivity in Whole Blood and Saliva | Mean [14C] radioactivity t(last) values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity | The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ngEq/mL:ngEq/mL | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose. |
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| Primary | Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva | The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL:ngEq/mL | Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R]) | Mean fe%(R) values per urine collection period are presented as a percentage of the total [14C]-AZD2014 dose administered on Day 1. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Mean | Standard Deviation | % of total [14C]-AZD2014 dose | Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Renal Clearance (CL[R]) of AZD2014 From Plasma. | CL(R) of AZD2014 from plasma up to 168 h post-dose. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R]) | fe cum%(R) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Mean | Standard Deviation | Cumulative % of total [14C]-AZD2014 dose | Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Primary | Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f]) | fe cum%(f) by the end of each collection period is presented following administration of [14C]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. | The PK analysis population consisted of all evaluable patients who were dosed with [14C]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data. | Posted | Mean | Standard Deviation | Cumulative % of total [14C]-AZD2014 dose | Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period. |
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| Secondary | Number of AEs Experienced by Patients. | AEs (including serious AEs [SAEs]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented. | The safety analysis population consisted of all patients who received at least one dose of AZD2014 (radiolabelled or non-radiolabelled). | Posted | Number | Participants | From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period. |
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| Secondary | Best Overall Response (BOR) Assessment | Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD). PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression. | The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment. | Posted | Number | Participants | RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period. |
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| Secondary | Best Percentage Change in Tumour Size From Baseline | Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions. | The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment. Patients with available data are presented. | Posted | Median | Full Range | Percentage change in tumour size | RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period. |
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| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | [14C]-AZD2014 Then AZD2014 + Fulvestrant | Single Dose Period: Patients were given a single oral dose of [14C]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy. | 1 | 1 | 1 | 1 |
| Urinary Tract Infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Mononeuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Anal inflammation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Onychomadesis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
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| Stoma site erythema | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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Not provided
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| Title | Measurements |
|---|---|
|
| 2 h (n = 4) |
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| 3 h (n = 4) |
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| 4 h (n = 4) |
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| 6 h (n = 4) |
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| 8 h (n = 4) |
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| 12 h (n = 4) |
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| 24 h (n = 2) |
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| Title | Measurements |
|---|---|
|
| 6 h (n = 3) |
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| 8 h (n = 3) |
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| 10 h (n = 3) |
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| 12 h (n = 3) |
|
| Title | Measurements |
|---|---|
|
| 6 h (n = 4) |
|
| 8 h (n = 4) |
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| 10 h (n = 3) |
|
| 12 h (n = 2) |
|
| Title | Measurements |
|---|---|
|
| 2 h (n = 4) |
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| 3 h (n = 4) |
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| 4 h (n = 4) |
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| 6 h (n = 4) |
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| 8 h (n = 4) |
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| 12 h (n = 4) |
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| Title | Measurements |
|---|---|
|
| 2 h |
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| 3 h |
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| 4 h |
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| 6 h |
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| 8 h |
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| 12 h |
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| Title | Measurements |
|---|---|
|
| 6 h |
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| 8 h |
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| 10 h |
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| 12 - 24 h |
|
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| 24 - 48 h |
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|
| 48 - 72 h |
|
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| 72 - 96 h |
|
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| 96 - 120 h |
|
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| 120 - 144 h |
|
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| 144 - 168 h |
|
|
| Title | Measurements |
|---|---|
|
| 0 - 48 h |
|
| 0 - 72 h |
|
| 0 - 96 h |
|
| 0 - 120 h |
|
| 0 - 144 h |
|
| 0 - 168 h |
|
| Title | Measurements |
|---|---|
|
| 0 - 96 h |
|
| 0 - 120 h |
|
| 0 - 144 h |
|
| 0 - 168 h |
|
| Patients who experienced any SAE |
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| Patients who experienced any causally related SAE |
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| Patients who experienced fatal SAE |
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| Non-response: SD |
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| Non-response: Progression |
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| Non-response: Not evaluable |
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