A Randomized, Placebo-controlled, Double-blind Multicenter Phase II Study to Investigate the Protectivity and Efficacy of Metformin Against Steatosis in Combination With FOLFIRI and Cetuximab in Subjects With First-line Palliative Treated, KRAS-Wild-Type, Metastatic Colorectal Cancer
This multicenter randomized, placebo-controlled phase II study will enroll 132 first-line
palliative treated subjects with metastatic KRAS wild type CRC.
Wild-type KRAS is required for study entry. Further target-related parameters, based on
current scientific knowledge may be assessed.
Subjects are randomized to Arm A or Arm B Arm A: FOLFIRI in combination with cetuximab and
metformin Arm B: FOLFIRI in combination with cetuximab and placebo
A liver biopsy of hepatic metastasis and normal liver tissue is planned before the first
cycle and at the end of treatment; with regard to the primary study objective, these
subjects are evaluable.
Both efficacy and safety data will be collected. The investigators will assess response to
treatment every 8 weeks based on imaging.
Following permanent treatment cessation, subjects will be followed-up for survival.
One interim analysis for futility (54 evaluable patients) and in addition two safety
analysis for evaluation of reported adverse events between the two treatment groups will be
performed at two different timepoints (20 evaluable patients/54 evaluable patients).
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Reduction in the chemotherapy-associated steatosis
Reduction in the chemotherapy-associated steatosis, as assessed by the steatosis subcore of NAFLD activity score (NAS)
up to 24 weeks
Birgit Gruenberger, MD
Austrian Breast & Colorectal Cancer Study Group
Austria: Federal Office for Safety in Health Care