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

Recurrent Melanoma Clinical Trial

Official title:

Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00866177
• Other study ID #: NCI-2009-01164
• Secondary ID: NCI-2009-01164MS
• Status: Completed
• Phase: Phase 2
• First received: March 19, 2009
• Last updated: July 16, 2015
• Start date: March 2009
• Est. completion date: September 2013

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Recurrent Melanoma
• Stage III Skin Melanoma
• Stage IV Skin Melanoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Selumetinib
Given orally

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST	Anti-tumor response defined as either a Complete Response, Partial Response, or Stable Disease as defined by RECIST	Up to 4 weeks	No