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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00866177
First received: March 19, 2009
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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 Melanoma
Stage IV Melanoma
Drug: selumetinib
Other: laboratory biomarker analysis
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 ]
    The response proportion for each cohort will be reported along with a 95% confidence interval.


Secondary Outcome Measures:
  • Response rates within various factors such as PTEN status [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Will be estimated. The 95% confidence intervals should also be provided.

  • Toxicity assessed using NCI Common Toxicity Grading system version 4.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: March 2009
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.
Drug: selumetinib
Given orally
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00866177

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Chapman Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00866177     History of Changes
Other Study ID Numbers: NCI-2009-01164, NCI-2009-01164, MSKCC-09003, CDR0000637669, 09-003, 8252, N01CM62206
Study First Received: March 19, 2009
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 16, 2014