MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma

NCT ID: NCT00866177

Last Updated: 2015-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2013-09-30

Brief Summary

This phase II trial is studying how well MEK inhibitor AZD6244 works in treating patients with stage III or stage IV melanoma. MEK inhibitor AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244.

SECONDARY OBJECTIVES:

I. Identify other genetic predictors of sensitivity to MEK inhibition.

OUTLINE: Patients are stratified according to pAKT expression (low vs high).

Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected for correlative laboratory studies. Samples are assessed for expression of pAKT, pPRAS40, and PTEN by IHC and mutations in BRAF, NRAS, KIT, and PIK3CAP by MALDI-TOF. PTEN is sequenced in tumors using whole genome amplification followed by high-throughput bidirectional dideoxynucleotide sequencing of PCR-amplified gene products.

After completion of study treatment, patients are followed for 4 weeks.

Conditions

Recurrent Melanoma; Stage III Skin Melanoma; Stage IV Skin Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Selumetinib

Intervention Type: DRUG

Given orally

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Selumetinib

Given orally

Intervention Type: DRUG

Other Intervention Names

ARRY-142886; AZD6244; MEK Inhibitor AZD6244

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed melanoma

• Stage IV or stage III disease not potentially curable with surgery
• Documented tumor progression
• Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• Must have tumor tissue (block or unstained slides) available for IHC studies
• No primary uveal or mucosal melanoma
• No active or untreated brain metastases

• Treated brain metastases allowed provided they have been stable for ≥ 3 months
• ECOG performance status 0-1
• Life expectancy > 3 months
• WBC ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment
• No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• No concurrent uncontrolled illness, including, but not limited to, any of the following:

• Ongoing or active infection or bleeding
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situation that would limit compliance with study requirements
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244
• Any number of prior therapies allowed
• At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• At least 4 months since prior anti-CTLA4 monoclonal antibody therapy
• At least 4 weeks since other prior systemic therapy
• No other concurrent investigational agents
• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E
• No concurrent anticancer chemotherapy or other systemic drugs
• Concurrent palliative radiotherapy allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Chapman

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2009-01164

Identifier Type: REGISTRY

Identifier Source: secondary_id

MSKCC-09003

Identifier Type: -

Identifier Source: secondary_id

CDR0000637669

Identifier Type: -

Identifier Source: secondary_id

09-003

Identifier Type: OTHER

Identifier Source: secondary_id

8252

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01164

Identifier Type: -

Identifier Source: org_study_id