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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: March 19, 2009
Last updated: July 16, 2015
Last verified: June 2013

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 Intervention Phase
Recurrent Melanoma
Stage III Skin Melanoma
Stage IV Skin Melanoma
Other: Laboratory Biomarker Analysis
Drug: Selumetinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Anti-tumor response defined as either a Complete Response, Partial Response, or Stable Disease as defined by RECIST

Enrollment: 167
Study Start Date: March 2009
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:


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.


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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00866177

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Paul Chapman Memorial Sloan Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00866177     History of Changes
Other Study ID Numbers: NCI-2009-01164, NCI-2009-01164, MSKCC-09003, CDR0000637669, 09-003, 8252, N01CM62206, P30CA008748
Study First Received: March 19, 2009
Results First Received: July 16, 2015
Last Updated: July 16, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas processed this record on October 08, 2015