A Randomized, Placebo-controlled, Double-blind Phase II Study Evaluating if Glucophage Can Avoid Liver Injury Due to Chemotherapy Associated Steatosis

• Status: Terminated
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This multicenter randomized, placebo-controlled phase II study will enroll 132 first-line palliative treated subjects with metastatic KRAS wild type CRC. Subjects with histologically confirmed, KRAS wild-type CRC without previous chemo-therapy for metastatic disease will be screened for this study.

Approximately 10 sites in Austria will participate in the study. Subjects will be randomized in a ratio of 1:1 into two groups.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Austrian Breast & Colorectal Cancer Study Group
• Collaborator: Merck Gesellschaft mbH, Austria
• Treatments: Cetuximab; Metformin

Criteria

Inclusion Criteria:

• Signed written informed consent

• Male or female >= 18 years of age

• Diagnosis of histologically confirmed, KRAS "wild-type" adenocarcinoma of the colon or rectum

• Non-resectable metastatic colorectal carcinoma

• Either presence of at least one liver lesion measurable unidimensionally by CT scan or MRI or at least one resectable liver metastasis with non-resectable extrahepatic disease (as assessed within 3 weeks prior to randomisation)

• Subjects scheduled to receive cetuximab and FOLFIRI

• ECOG performance status of 0 - 1 at study entry

• Leukocytes >= 3.0 x 10^9/L and neutrophils >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, and hemoglobin >= 8 g/dL

• Bilirubin <= 1.5 x ULN

• ASAT and ALAT <= 5 x ULN

Exclusion Criteria:

• Brain metastasis (if suspected, brain scan indicated)

• Previous chemotherapy for the currently existing metastatic disease

• Known or newly diagnosed diabetes

• Patients with ACS within the last three months

• Stage 3 or 4 heart failure defined according to the NYHA criteria

• Uncontrolled angina

• Contraindications to metformin (renal impairment [eGFR <45 mL/min/1.73m^2], known hypersensitivity to metformin, acute illness [dehydration, severe infection, shock, acute cardiac failure]), and suspected tissue hypoxia

• Surgery (excl. diagnostic biopsy, central venous catheter) or irradiation within 2 weeks prior to study entry defined as given written informed consent

• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol

• Administration of any investigational agent(s) within 4 weeks prior to study entry,

• Previous exposure to EGFR-pathway targeting therapy

• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

• Known grade 3 or 4 allergic reaction to any of the components of the treatment

• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Subjects with a previous malignancy but without evidence of disease for >= 5 years will be allowed to enter the trial)

• Pregnancy or lactation

• Inadequate contraception (male or female patients) if of childbearing or procreative potential

• Known drug abuse/ alcohol abuse

• Legal incapacity or limited contractual capacity Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent