09CRC02 Study Summary
PROTOCOL SUMMARY:
Title:
A Dose Finding and Phase II Study of AZD6244 (Hyd-Sulfate) in Combination with Irinotecan in 2nd Line Patients with K-ras or B-raf Mutation Positive Advanced or Metastatic Colorectal Cancer.
Primary Objective:
Part A: To determine the phase II dose of AZD6244 when administered in combination with Irinotecan in 2nd line patients with K-ras or B-raf mutation positive advanced or metastatic colorectal cancer (CRC).
Part B: To assess the efficacy in terms of Objective Response Rate (ORR) of AZD6244 in combination with irinotecan in 2sup>nd line patients with K-ras or B-raf mutation positive advanced or metastatic CRC.
Secondary Objectives:
To assess the safety of the combination of AZD6244 with irinotecan.
To investigate the PK of AZD6244, N-desmethyl AZD6244, and AZD6244 amide when administered in combination with irinotecan.
To assess progression free survival (PFS) for patients with K-ras or B-raf mutated colorectal cancers treated with combination of irinotecan and AZD6244.
Exploritory Objectives:
To investigate the relationship between AZD6244 and/or N-desmethyl AZD6244 and AZD6244 amide plasma concentrations/exposure and clinical outcomes, efficacy, AEs and other safety parameters, as appropriate.
To explore pharmacodiagnostic (baseline/predictive) and pharmacodynamic (post-treatment) biomarkers in tumor tissue in patients treated with AZD6244 and irinotecan.
Target Population:
Second line patients, aged 18 and higher, with K-ras or B-raf mutated advanced or metastatic CRC progressing after first line therapy with an oxaliplatin based regimen and bevacizumab. Patients must have measurable disease and ECOG Performance Status of 0-1.
Rationale for Drug Combination:
Pre-clinical studies with AZD6244 and clinical experience to date suggest that cell lines and tumors with activating mutations in Ras/Raf/MEK/ERK transduction pathway may be particularly sensitive to MEK inhibition. Over-activated MAPK pathway has been implicated in numerous cancers, including CRC with pertaining K-ras mutations. Indeed, mutations of the MAPK, Ras/Raf/MEK/ERK signaling pathways are found in approximately 90% of all stage IV sporadic colorectal cancers. Specifically, as this protocol will target only patients with K-ras or B-raf mutations, these are found in 45-50% of sporadic stage four colon cancers. As this group will be resistant to the EGFR inhibitors, cetuximab and panitumimab, it is particularly important to define effective second-line treatments for this subgroup.
Enrollment Period:
April 2010 to November 2011.
Contact Information:
General AGICC contact:
Patricia Ames: (323) 966-3564
See Site Specific contacts below:
For more detailed study information, see www.clinicaltrials.gov; Trial Identifier: NCT01116271
This clinical research trial is open or will be opening at the following AGICC sites:
Christiana Care Helen F. Graham Cancer Center
PI: Bruce M. Boman, MD
Phone Number: (302) 623-4550
Comprehensive Cancer Center at Desert Regional Medical Center
PI: Lawrence P. Leichman, MD
Phone Number: (760) 416-4734
Fox Chase Cancer Center
PI: Crystal Denlinger, MD
Phone Number: (215) 728-2689
Keck School of Medicine, University of Southern California
PI: Heinz-Josef Lenz, MD
Phone Number: (323) 865-3955
Mount Sinai Comprehensive Cancer Center
PI: Joseph Pizzolato, MD
Phone Number: (305) 535-3390
NYU Cancer Institute at NYU Langone Medical Center
PI: Deirdre Cohen, MD
Phone Number: (212) 731-5656
Swedish Cancer Institute
PI: Philip J. Gold, MD
Phone Number: (206) 386-2121
University of Colorado Cancer Center
PI: S. Gail Eckhardt, MD
Phone Number: (303) 724-3850
University of North Carolina Lineberger Comprehensive Cancer Center
PI: Bert H. O’Neil, MD
Phone Number: (919) 843-7115
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