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

Primary Purpose

Recurrent Melanoma, Stage III Skin Melanoma, Stage IV Skin Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Selumetinib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
March 19, 2009
Last Updated
July 16, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00866177
Brief Title
MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma
Official Title
Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage III Skin Melanoma, Stage IV Skin Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
167 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Selumetinib
Other Intervention Name(s)
ARRY-142886, AZD6244, MEK Inhibitor AZD6244
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST
Description
Anti-tumor response defined as either a Complete Response, Partial Response, or Stable Disease as defined by RECIST
Time Frame
Up to 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Chapman
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

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

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