AZD6244 (ARRY-142886) Solid Oral Dosage Formulation in Participants With Advanced Solid Malignancies

NCT00463814 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: D1532C000052022-500685-10-002006-004497-26
• Study Type: interventional
• Target: 58
• Locations: 3 countries
• Sites: 4

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.

Conditions

Tumor; Cancer

Keywords

Advanced Malignancy; Cancer Eligibility; Malignancy

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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).

  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.

  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.

  Day 1 through 11.8 months (maximum observed duration)

Secondary Outcomes (44)

• 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

• 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

• 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

• 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

• 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

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: AZD6244

Interventions

AZD6244 DRUG

Participants will receive single oral dose of AZD6244 as described in arm description.

Also known as: ARRY-142886

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

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Nijmegen, 6525 GA, Netherlands

Location

Research Site

Utrecht, 3584 CX, Netherlands

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 22293660 DERIVED

Related Links

• CSR\_redacted\_2023
• Study Results

MeSH Terms

Conditions

Neoplasms

Interventions

AZD 6244

Study Officials

• Emerging Oncology Medical Science Director, MD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 20, 2007
• Study Start: March 8, 2007
• Primary Completion: June 17, 2008
• Study Completion: December 31, 2025
• Last Updated: November 13, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (1); NL (2); GB (1)