TumorPhase 1NCT00463814
AZD6244 (ARRY-142886) Solid Oral Dosage Formulation in Participants With Advanced Solid Malignancies
A Phase 1 study testing AZD6244 in people with Tumor and Cancer, run by AstraZeneca at 4 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 99 years
- What is being tested?
- AZD6244
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 8 Mar 2007to 26 Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Netherlands2 sites
Research Site
Nijmegen, 6525 GA
Research Site
Utrecht, 3584 CX
About this study
Official title: A Phase I, Open-Label, Multi-centre Study to Assess the Safety, Tolerability and Pharmacokinetics of a Solid Oral Dosage Formulation (Capsule) of AZD6244 in Patients With Advanced Solid Malignancies
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
- Being tested
- AZD6244
- Keywords
- Advanced Malignancy, Cancer Eligibility, Malignancy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD6244Drug
Also called ARRY-142886
Participants will receive single oral dose of AZD6244 as described in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Dose Escalation AZD6244 25 mg | Experimental | Participants will receive a single oral dose of AZD6244 25 mg capsule on Day 1 followed by continuous twice daily (bd) dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
| Part A: Dose Escalation AZD6244 50 mg | Experimental | Participants will receive a single oral dose of AZD6244 50 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
| Part A: Dose Escalation AZD6244 75 mg | Experimental | Participants will receive a single oral dose of AZD6244 75 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
| Part A: Dose Escalation AZD6244 100 mg | Experimental | Participants will receive a single oral dose of AZD6244 100 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
| Part B: Relative Bioavailability (Sequence 1) and Safety Assessment Phase | Experimental | Participants in relative bioavailability phase will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 75 mg capsule on Day 8 (Sequence 1). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
| Part B: Relative Bioavailability (Sequence 2) and Safety Assessment Phase | Experimental | Participants in relative bioavailability phase will receive a single oral dose of AZD6244 75 mg capsule on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 8 (Sequence 2). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. Receives: Drug: AZD6244 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Part A and Part B
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.
Measured: Day 1 through 11.8 months (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Part A and Part B
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.
Measured: Day 1 through 11.8 months (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A and Part B
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).
Measured: Day 1 through 11.8 months (maximum observed duration)
Number of Participants With Abnormal Echocardiogram (ECHO) Parameters Reported as TEAEs in Part A and Part B
Number of participants with abnormal ECHO parameters reported as TEAEs are reported.
Measured: Day 1 through 11.8 months (maximum observed duration)
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Part A and Part B
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
Measured: Day 1 through 11.8 months (maximum observed duration)
Secondary outcomes (44)
Maximum Plasma Concentration (Cmax) of AZD6244 (Part A)
The Cmax of AZD6244 in Part A is reported.
Measured: 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
Cmax of AZD6244 (Part B Single 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.
Measured: 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
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) of AZD6244 (Part A)
The AUC of AZD6244 in Part A is reported.
Measured: 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
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC[0-12]) of AZD6244 (Part A)
The AUC(0-12) of AZD6244 in Part A is reported.
Measured: 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
AUC of AZD6244 (Part B Single 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.
Measured: 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
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of AZD6244 (Part B Single 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.
Measured: 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
Time to Reach Maximum Plasma Concentration (Tmax) of AZD6244 (Part A)
The Tmax of AZD6244 in Part A is reported.
Measured: 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
Tmax of AZD6244 (Part B Single 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.
Measured: 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
Half-life (t1/2) of AZD6244 (Part A)
The t1/2 of AZD6244 in Part A is reported.
Measured: 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
t1/2 of AZD6244 (Part B Single 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.
Measured: 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
Total Apparent Drug Clearance (CL/F) of AZD6244 (Part A)
The CL/F of AZD6244 in Part A is reported.
Measured: 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
CL/F of AZD6244 (Part B Single 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.
Measured: 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
Volume of Distribution at Steady State (Vss/F) of AZD6244 (Part A)
The Vss/F of AZD6244 in Part A is reported.
Measured: 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
Vss/F of AZD6244 (Part B Single 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.
Measured: 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
Cmax of N-desmethyl AZD6244 (Part A)
The Cmax of N-desmethyl AZD6244 in Part A is reported.
Measured: 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
Cmax of N-desmethyl AZD6244 (Part B Single 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.
Measured: 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
AUC of N-desmethyl AZD6244 (Part A)
The AUC of N-desmethyl AZD6244 in Part A is reported.
Measured: 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
AUC(0-12) of N-desmethyl AZD6244 (Part A)
The AUC(0-12) of N-desmethyl AZD6244 in Part A is reported.
Measured: 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
AUC of N-desmethyl AZD6244 (Part B Single 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.
Measured: 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
AUC(0-24) of N-desmethyl AZD6244 (Part B Single 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.
Measured: 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
Tmax of N-desmethyl AZD6244 (Part A)
The Tmax of N-desmethyl AZD6244 in Part A is reported.
Measured: 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
Tmax of N-desmethyl AZD6244 (Part B Single 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.
Measured: 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
t1/2 of N-desmethyl AZD6244 (Part A)
The t1/2 of N-desmethyl AZD6244 in Part A is reported.
Measured: 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
t1/2 of N-desmethyl AZD6244 (Part B Single 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.
Measured: 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
Cmax of AZD6244 Amide (Part A)
The Cmax of AZD6244 amide in Part A is reported.
Measured: 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
Cmax of AZD6244 Amide (Part B Single 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.
Measured: 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
AUC(0-12) of AZD6244 Amide (Part A)
The AUC(0-12) of AZD6244 amide in Part A is reported.
Measured: 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
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)
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.
Measured: 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
AUC(0-24) of AZD6244 Amide (Part B Single 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.
Measured: 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
Tmax of AZD6244 Amide (Part A)
The Tmax of AZD6244 amide in Part A is reported.
Measured: 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
Tmax of AZD6244 Amide (Part B Single 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.
Measured: 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
Cmax of AZD6244 (Part B Multiple Doses)
The Cmax of AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Tmax of AZD6244 (Part B Multiple Doses)
The Tmax of AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-4) of AZD6244 (Part B Multiple Doses)
The AUC(0-4) of AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
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)
The AUC(0-t) of AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Cmax of N-desmethyl AZD6244 (Part B Multiple Doses)
The Cmax of N-desmethyl AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Tmax of N-desmethyl AZD6244 (Part B Multiple Doses)
The Tmax of N-desmethyl AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-4) of N-desmethyl AZD6244 (Part B Multiple Doses)
The AUC(0-4) of N-desmethyl AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-t) of N-desmethyl AZD6244 (Part B Multiple Doses)
The AUC(0-t) of N-desmethyl AZD6244 in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Cmax of AZD6244 Amide (Part B Multiple Doses)
The Cmax of AZD6244 amide in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Tmax of AZD6244 Amide (Part B Multiple Doses)
The Tmax of AZD6244 amide in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-4) of AZD6244 Amide (Part B Multiple Doses)
The AUC(0-4) of AZD6244 amide in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-t) of AZD6244 Amide (Part B Multiple Doses)
The AUC(0-t) of AZD6244 amide in Part B is reported.
Measured: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Percentage Inhibition of Extracellular Signal-regulated Kinase (ERK) Phosphorylation
Percentage inhibition of ERK phosphorylation is reported.
Measured: 1, 4, 8, and 24 hours post-dose on Day 1 (Part A and Part B) and Day 8 (Part B)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2007 (estimated)
- Study start8 Mar 2007
- Primary completion17 Jun 2008
- Study completion26 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TumorStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Emerging Oncology Medical Science Director, MD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00463814
- Sponsor's protocol ID
- D1532C00005
- Other IDs
- 2022-500685-10-00, 2006-004497-26
- Status last verified
- Aug 2026
- First submitted
- 18 Apr 2007
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
Boers-Sonderen MJ, Desar IM, Blokx W, Timmer-Bonte JN, van Herpen CM. A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244). Anticancer Drugs. 2012 Aug;23(7):761-4. doi: 10.1097/CAD.0b013e328350737d.
PubMed 22293660
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Multi-centre Study to Assess the Safety, Tolerability and Pharmacokinetics of a Solid Oral Dosage Formulation (Capsule) of AZD6244 in Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT00463814
- Acronym / sponsor ID
- D1532C00005
- Keywords
- Advanced Malignancy, Cancer Eligibility, Malignancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 58 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2007 (actual)
- Primary completion
- 17 Jun 2008 (actual)
- Study completion
- 26 Mar 2027 (estimated)
- First posted
- 20 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A: Dose Escalation AZD6244 25 mg | Experimental | Drug: AZD6244Participants will receive a single oral dose of AZD6244 25 mg capsule on Day 1 followed by continuous twice daily (bd) dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
| Part A: Dose Escalation AZD6244 50 mg | Experimental | Drug: AZD6244Participants will receive a single oral dose of AZD6244 50 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
| Part A: Dose Escalation AZD6244 75 mg | Experimental | Drug: AZD6244Participants will receive a single oral dose of AZD6244 75 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
| Part A: Dose Escalation AZD6244 100 mg | Experimental | Drug: AZD6244Participants will receive a single oral dose of AZD6244 100 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
| Part B: Relative Bioavailability (Sequence 1) and Safety Assessment Phase | Experimental | Drug: AZD6244Participants in relative bioavailability phase will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 75 mg capsule on Day 8 (Sequence 1). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
| Part B: Relative Bioavailability (Sequence 2) and Safety Assessment Phase | Experimental | Drug: AZD6244Participants in relative bioavailability phase will receive a single oral dose of AZD6244 75 mg capsule on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 8 (Sequence 2). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD6244Also: ARRY-142886Participants will receive single oral dose of AZD6244 as described in arm description. | Drug | Part A: Dose Escalation AZD6244 100 mg, Part A: Dose Escalation AZD6244 25 mg, Part A: Dose Escalation AZD6244 50 mg, Part A: Dose Escalation AZD6244 75 mg, Part B: Relative Bioavailability (Sequence 1) and Safety Assessment Phase, Part B: Relative Bioavailability (Sequence 2) and Safety Assessment Phase |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Part A and Part B
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 through 11.8 months (maximum observed duration)
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
44 secondary outcomes
Maximum Plasma Concentration (Cmax) of AZD6244 (Part A)
Time frame: 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
Cmax of AZD6244 (Part B Single Dose)
Time frame: 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
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) of AZD6244 (Part A)
Time frame: 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
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC[0-12]) of AZD6244 (Part A)
Time frame: 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
AUC of AZD6244 (Part B Single Dose)
Time frame: 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
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC[0-24]) of AZD6244 (Part B Single Dose)
Time frame: 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
Time to Reach Maximum Plasma Concentration (Tmax) of AZD6244 (Part A)
Time frame: 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
Tmax of AZD6244 (Part B Single Dose)
Time frame: 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
Half-life (t1/2) of AZD6244 (Part A)
Time frame: 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
t1/2 of AZD6244 (Part B Single Dose)
Time frame: 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
Total Apparent Drug Clearance (CL/F) of AZD6244 (Part A)
Time frame: 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
CL/F of AZD6244 (Part B Single Dose)
Time frame: 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
Volume of Distribution at Steady State (Vss/F) of AZD6244 (Part A)
Time frame: 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
Vss/F of AZD6244 (Part B Single Dose)
Time frame: 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
Cmax of N-desmethyl AZD6244 (Part A)
Time frame: 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
Cmax of N-desmethyl AZD6244 (Part B Single Dose)
Time frame: 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
AUC of N-desmethyl AZD6244 (Part A)
Time frame: 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
AUC(0-12) of N-desmethyl AZD6244 (Part A)
Time frame: 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
AUC of N-desmethyl AZD6244 (Part B Single Dose)
Time frame: 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
AUC(0-24) of N-desmethyl AZD6244 (Part B Single Dose)
Time frame: 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
Tmax of N-desmethyl AZD6244 (Part A)
Time frame: 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
Tmax of N-desmethyl AZD6244 (Part B Single Dose)
Time frame: 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
t1/2 of N-desmethyl AZD6244 (Part A)
Time frame: 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
t1/2 of N-desmethyl AZD6244 (Part B Single Dose)
Time frame: 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
Cmax of AZD6244 Amide (Part A)
Time frame: 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
Cmax of AZD6244 Amide (Part B Single Dose)
Time frame: 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
AUC(0-12) of AZD6244 Amide (Part A)
Time frame: 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
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)
Time frame: 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
AUC(0-24) of AZD6244 Amide (Part B Single Dose)
Time frame: 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
Tmax of AZD6244 Amide (Part A)
Time frame: 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
Tmax of AZD6244 Amide (Part B Single Dose)
Time frame: 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
Cmax of AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Tmax of AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-4) of AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
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)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Cmax of N-desmethyl AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Tmax of N-desmethyl AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-4) of N-desmethyl AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
AUC(0-t) of N-desmethyl AZD6244 (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Cmax of AZD6244 Amide (Part B Multiple Doses)
Time frame: Days 15 and 22: Pre-dose (within 10 minutes of dosing); 1, 2, and 4 hours post-dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Derived from this study: PubMed 22293660Boers-Sonderen MJ, Desar IM, Blokx W, Timmer-Bonte JN, van Herpen CM. A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244). Anticancer Drugs. 2012 Aug;23(7):761-4. doi: 10.1097/CAD.0b013e328350737d.
- CSR\_redacted\_2023Link provided by the sponsor.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emerging Oncology Medical Science Director, MD study director
AstraZeneca
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD6244 in people with Tumor and Cancer, run by AstraZeneca at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Part A and Part B (time frame: Day 1 through 11.8 months (maximum observed duration)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00463814, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.