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

• ClinicalTrials.gov Identifier: NCT00866177
• Recruitment Status: Completed
• First Posted: March 20, 2009
• Results First Posted: August 11, 2015
• Last Update Posted: August 11, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Melanoma; Stage III Skin Melanoma; Stage IV Skin Melanoma	Other: Laboratory Biomarker Analysis; Drug: Selumetinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 167 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
• Study Start Date: March 2009
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Selumetinib; Given orally; Other Names: ARRY-142886; AZD6244; MEK Inhibitor AZD6244

Outcome Measures

Primary Outcome Measures :

1. Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST [ Time Frame: Up to 4 weeks ]
   Anti-tumor response defined as either a Complete Response, Partial Response, or Stable Disease as defined by RECIST

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Chapman; Memorial Sloan Kettering Cancer Center

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00866177
• Other Study ID Numbers: NCI-2009-01164; NCI-2009-01164 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MSKCC-09003; CDR0000637669; 09-003 ( Other Identifier: Memorial Sloan-Kettering Cancer Center ); 8252 ( Other Identifier: CTEP ); N01CM62206 ( U.S. NIH Grant/Contract ); P30CA008748 ( U.S. NIH Grant/Contract )
• First Posted: March 20, 2009
• Results First Posted: August 11, 2015
• Last Update Posted: August 11, 2015
• Last Verified: June 2013

Additional relevant MeSH terms:

Melanoma; Skin Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases