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

Austrian Breast & Colorectal Cancer Study Group

Status and phase

Terminated

Phase 2

Conditions

Steatohepatitis

Colorectal Cancer

Treatments

Drug: Metformin/Placebo

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT01523639

2011-001010-34 (EudraCT Number)

G-LUCAS

200084-610 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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).

Enrollment

8 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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