Selumetinib in Cancers With BRAF Mutations
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.
Unspecified Adult Solid Tumor, Protocol Specific
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis|
- Objective response rate in patients with cancers other than melanoma [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]Will be estimated using Kaplan-Meier survival curves. Confidence intervals will be calculated and reported.
- Objective response rate in patients with non-small cell lung cancers and colon cancers [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]95% CI will be provided for overall and subgroups rates.
- AKT pathway activity [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
- Sensitivity and specificity of detection of the BRAF V600E mutation in CTC using the CTC-chip [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
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.
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').
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.
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Massachusetts General Hospital|
|Charlestown, Massachusetts, United States, 02129|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Donald Lawrence||Massachusetts General Hospital|