Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis
Overview
- Phase
- Phase 2
- Intervention
- Selumetinib
- Conditions
- Adult Solid Neoplasm
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 28
- Locations
- 5
- Primary Endpoint
- Objective Response Rate in Patients With Cancers Other Than Melanoma
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this research study is to determine if selumetinib is safe and effective in treating patients with cancers with a mutated BRAF gene. Selumetinib is an investigational drug that works by blocking a protein called MEK, which is known to play a role in the growth of cancer cells lines and tumors that have a mutated BRAF gene. There are multiple types of cancers that have mutations in the BRAF gene and depend on the activity of this gene for their growth and survival.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the objective response rate to AZD6244 (selumetinib) in patients with cancers other than melanoma in which BRAF mutations have been identified prospectively. SECONDARY OBJECTIVES: I. To evaluate progression-free survival in subjects treated with AZD6244. II. To obtain a preliminary estimate of the objective response rate in non-small cell lung cancers and colon cancers with BRAF mutations. III. To explore biologic correlates of responsiveness to AZD6244, and specifically to correlate AKT pathway activity with sensitivity to MEK inhibition in the BRAF mutant class of tumors. IV. To estimate the sensitivity and specificity of detection of the BRAF V600E mutation in circulating tumor cells (CTC) using a microfluidic platform (the 'CTC-chip'). OUTLINE: Patients receive selumetinib orally (PO) twice daily (BID) for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and willingness to sign a written informed consent document
- •Histologically confirmed metastatic or unresectable solid tumor
- •Results from tumor tissue analysis that show a glutamic acid-for-valine substitution at amino acid position 600 in the BRAF gene (V600E) or other activating BRAF mutation, as determined by high-throughput genotyping
- •Patients may have received any number of prior systemic treatments for their cancer
- •At least one measurable site of disease by CT, according to standard RECIST criteria 1.0
- •ECOG performance status 0-1
- •Absolute neutrophil count \> 1500 per cubic mm
- •Platelet count \> 100,000 per cubic mm
- •Hemoglobin \> 9 g/dl
- •Serum bilirubin \< 1.5 x upper limit of normal
Exclusion Criteria
- •Estimated life expectancy \> 12 weeks
- •Patients with melanoma
- •Have received chemotherapy or radiotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C), or a targeted therapy within 2 weeks prior to entering the study
- •Have not recovered from adverse events due to agents previously administered (CTCAE v3 grade 1 or baseline)
- •Currently receiving other investigational agents
- •Known brain metastases, unless treated and stable off of corticosteroids for at least four weeks
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
- •Prior treatment with a selective inhibitor of RAF or MEK (e.g., RAF265); (note: prior sorafenib is allowed)
- •Uncontrolled intercurrent illness, including but not limited to:
- •Clinically significant active infection
Arms & Interventions
Treatment (selumetinib)
Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Selumetinib
Outcomes
Primary Outcomes
Objective Response Rate in Patients With Cancers Other Than Melanoma
Time Frame: 4 years
Percentage of participants achieving either complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, when compared with baseline) using CT (computed tomography) scans (which are done every 6 weeks).
Secondary Outcomes
- AKT Pathway Activity(Up to 4 years)
- Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers(Up to 4 years)
- Progression-free Survival(4 months)
- Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip(Up to 4 years)