Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
18 Years
N/A
Both
Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma
Trial Information
Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Anti-tumor response defined as either a CR, PR, or SD as defined by RECIST
Outcome Description:
The response proportion for each cohort will be reported along with a 95% confidence interval.
Outcome Time Frame:
Up to 4 weeks
Safety Issue:
No
Principal Investigator
Paul Chapman
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-01164
NCT ID:
NCT00866177
Start Date:
March 2009
Completion Date:
Related Keywords:
- Recurrent Melanoma
- Stage III Melanoma
- Stage IV Melanoma
- Melanoma
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
