A randomized, placebo-controlled, double-blind phase II study evaluating if Glucophage can avoid Liver injury due to Chemotherapy Associated Steatosis.
- Conditions
- first-line palliative treated, KRAS-Wild-Type, metastatic colorectal cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001010-34-AT
- Lead Sponsor
- ABCSG (Austrian Breast & Colorectal Cancer Study Group)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 132
• 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132
• 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Reduction in chemo-therapy associated steatosis in subjects with first-line palliative treatment of metastatic colorectal cancer;Secondary Objective: - To evaluate the safety and tolerability of metformin in combination with FOLFIRI and cetuximab as first line therapy for KRAS wild-type mCRC by recording the adverse events and abnormal laboratory values associated with the study treatments.<br>- To assess the efficacy of of metformin in combination with FOLFIRI and cetuximab as first line therapy for KRAS wild-type mCRC with respect to tumour response rate, progression free survival and overall survival.<br>- Reduction in chemo-therapy associated steatohepatitis in subjects with first-line palliative treatment of mCRC<br>;Primary end point(s): Reduction in the chemotherapy-associated steatosis, as assessed by the steatosis subcore of NAFLD activity score (NAS);Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated after the last treatment visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Progression free survival (PFS)<br>• Overall survivial (OS)<br>• Safety / Adverse events (all subjects received at least one dose of IMP)<br>• Objective response rate (CR/PR), as assessed by RECIST criteria, version 1.1<br>• Reduction in chemo-therapy associated steatohepatitis (CASH) as assessed by NAS;Timepoint(s) of evaluation of this end point: • PFS and OS will be evaluated after final study visits. Subjects who terminate the study before their scheduled final study visits will be censored.<br>• Safety outcomes will be evaluated after the last treatment visit, adverse events will be evaluated after the final study visit. Additional safety analyses of reported AEs will be performed after the evaluation of 20 and 54 patients (between the 2 treatment groups) at the time of interim analysis.<br>• The objective response rate and the reduction in NAS will be evaluated after the last treatment visit.