Cancer, Tumor
Conditions
Keywords
Advanced Malignancy, Cancer Eligibility, Malignancy
Brief summary
The primary purpose of the study is to assess the safety, tolerability and pharmacokinetics of a capsule of AZD6244 in participants with advanced solid malignancies
Interventions
DRUGAZD6244
Participants will receive single oral dose of AZD6244 as described in arm description.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* cancer which is refractory to standard therapies * World Health Organization (WHO) performance status 0 to 2 * evidence of post-menopausal status or negative pregnancy test
Exclusion criteria
* Radiotherapy/chemotherapy within 21 days prior to entry * brain metastases/spinal cord compression unless stable off steroids/anticonvulsants * evidence of severe/uncontrolled systemic disease * participated in an investigational drug study within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Part A and Part B | Day 1 through 11.8 months (maximum observed duration) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Part A and Part B | Day 1 through 11.8 months (maximum observed duration) | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, and urinalysis. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A and Part B | Day 1 through 11.8 months (maximum observed duration) | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, oxygen saturation, weight, and pulse rate). |
| Number of Participants With Abnormal Echocardiogram (ECHO) Parameters Reported as TEAEs in Part A and Part B | Day 1 through 11.8 months (maximum observed duration) | Number of participants with abnormal ECHO parameters reported as TEAEs are reported. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Part A and Part B | Day 1 through 11.8 months (maximum observed duration) | Number of participants with abnormal ECG parameters reported as TEAEs are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Cmax of AZD6244 in Part A is reported. |
| Cmax of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Cmax of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC of AZD6244 in Part A is reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC[0-12]) of AZD6244 (Part A) | Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The AUC(0-12) of AZD6244 in Part A is reported. |
| AUC of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC(0-24) of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Time to Reach Maximum Plasma Concentration (Tmax) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Tmax of AZD6244 in Part A is reported. |
| Tmax of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Tmax of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Half-life (t1/2) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The t1/2 of AZD6244 in Part A is reported. |
| t1/2 of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The t1/2 of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Total Apparent Drug Clearance (CL/F) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The CL/F of AZD6244 in Part A is reported. |
| CL/F of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The CL/F of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Volume of Distribution at Steady State (Vss/F) of AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Vss/F of AZD6244 in Part A is reported. |
| Vss/F of AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Vss/F of AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Cmax of N-desmethyl AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Cmax of N-desmethyl AZD6244 in Part A is reported. |
| Cmax of N-desmethyl AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Cmax of N-desmethyl AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| AUC of N-desmethyl AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC of N-desmethyl AZD6244 in Part A is reported. |
| AUC(0-12) of N-desmethyl AZD6244 (Part A) | Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The AUC(0-12) of N-desmethyl AZD6244 in Part A is reported. |
| AUC of N-desmethyl AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC of N-desmethyl AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| AUC(0-24) of N-desmethyl AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC(0-24) of N-desmethyl AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Tmax of N-desmethyl AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Tmax of N-desmethyl AZD6244 in Part A is reported. |
| Tmax of N-desmethyl AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Tmax of N-desmethyl AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| t1/2 of N-desmethyl AZD6244 (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The t1/2 of N-desmethyl AZD6244 in Part A is reported. |
| t1/2 of N-desmethyl AZD6244 (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The t1/2 of N-desmethyl AZD6244 in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Cmax of AZD6244 Amide (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Cmax of AZD6244 amide in Part A is reported. |
| Cmax of AZD6244 Amide (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Cmax of AZD6244 amide in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| AUC(0-12) of AZD6244 Amide (Part A) | Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The AUC(0-12) of AZD6244 amide in Part A is reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post Dose (AUC[0-4]) of AZD6244 Amide (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC(0-4) of AZD6244 amide in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| AUC(0-24) of AZD6244 Amide (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The AUC(0-24) of AZD6244 amide in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Tmax of AZD6244 Amide (Part A) | Day 1: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose; Day 8: Pre-dose (within 10 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, and 12 hours post-dose | The Tmax of AZD6244 amide in Part A is reported. |
| Tmax of AZD6244 Amide (Part B Single Dose) | Days 1 and 8: Pre-dose (within 30 minutes of dosing); 5, 15, and 30 minutes, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose | The Tmax of AZD6244 amide in Part B is reported. Day 1 and Day 8 in Part B are the first days of two periods in crossover bioavailability assessment of two AZD6244 formulations: capsule versus the free-base suspension. |
| Cmax of AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Cmax of AZD6244 in Part B is reported. |
| Tmax of AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Tmax of AZD6244 in Part B is reported. |
| AUC(0-4) of AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-4) of AZD6244 in Part B is reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC[0-t]) of AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-t) of AZD6244 in Part B is reported. |
| Cmax of N-desmethyl AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Cmax of N-desmethyl AZD6244 in Part B is reported. |
| Tmax of N-desmethyl AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Tmax of N-desmethyl AZD6244 in Part B is reported. |
| AUC(0-4) of N-desmethyl AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-4) of N-desmethyl AZD6244 in Part B is reported. |
| AUC(0-t) of N-desmethyl AZD6244 (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-t) of N-desmethyl AZD6244 in Part B is reported. |
| Cmax of AZD6244 Amide (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Cmax of AZD6244 amide in Part B is reported. |
| Tmax of AZD6244 Amide (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The Tmax of AZD6244 amide in Part B is reported. |
| AUC(0-4) of AZD6244 Amide (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-4) of AZD6244 amide in Part B is reported. |
| AUC(0-t) of AZD6244 Amide (Part B Multiple Doses) | Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose | The AUC(0-t) of AZD6244 amide in Part B is reported. |
| Percentage Inhibition of Extracellular Signal-regulated Kinase (ERK) Phosphorylation | 1, 4, 8, and 24 hours post-dose on Day 1 (Part A and Part B) and Day 8 (Part B) | Percentage inhibition of ERK phosphorylation is reported. |
Countries
Netherlands, United Kingdom, United States
Contacts
STUDY_DIRECTOREmerging Oncology Medical Science Director, MD
AstraZeneca
Outcome results
None listed