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

AstraZeneca

Status and phase: Active, not recruiting; Phase 1

Conditions: Cancer; Tumor

Treatments: Drug: AZD6244

Study type: Interventional

Funder types: Industry

Identifiers

NCT00463814

D1532C00005

2022-500685-10-00 (Registry Identifier)

2006-004497-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 58 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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58 participants in 6 patient groups

Part A: Dose Escalation AZD6244 25 mg

Experimental group

Description:

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.

Treatment:

Drug: AZD6244

Part A: Dose Escalation AZD6244 50 mg

Experimental group

Description:

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.

Treatment:

Drug: AZD6244

Part A: Dose Escalation AZD6244 75 mg

Experimental group

Description:

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.

Treatment:

Drug: AZD6244

Part A: Dose Escalation AZD6244 100 mg

Experimental group

Description:

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.

Treatment:

Drug: AZD6244

Part B: Relative Bioavailability (Sequence 1) and Safety Assessment Phase

Experimental group

Description:

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.

Treatment:

Drug: AZD6244

Part B: Relative Bioavailability (Sequence 2) and Safety Assessment Phase

Experimental group

Description:

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.

Treatment:

Drug: AZD6244