G-Lucas Details

A randomized, placebo-controlled, multicenter phase-II-study to investigate the protectivity and efficacy of metformin in combination with FOLFIRI and cetuximab in patients with previously untreated, KRAS-wild-type, metastatic colorectal cancer

Start:
04/2012

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

G-Lucas Design
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Primary objectives:

  • Reduction in chemo-therapy associated steatosis in subjects with first-line palliative treatment of mCRC

Secondary objectives:

  • 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
  • To assess the efficacy 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
  • Reduction in chemo-therapy associated steatohepatitis in subjects with first-line palliative treatment of mCRC

Inclusion criteria:

  1. Signed written informed consent
  2. Male or female ³ 18 years of age
  3. Diagnosis of histologically confirmed, KRAS “wild-type” adenocarcinoma of the colon or rectum
  4. Non-resectable metastatic colorectal carcinoma
  5. 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); further details please refer to 6.1
  6. Subjects scheduled to receive cetuximab and FOLFIRI
  7. ECOG performance status of 0 – 1 at study entry
  8. Leukocytes ³ 3.0 x 109/L and neutrophils ³ 1.5 x 109/L, platelets ³ 100 x 109/L, and hemoglobin ³ 8 g/dL
  9. Bilirubin £ 1.5 x ULN
  10. ASAT and ALAT £ 5 x ULN

Exclusion criteria:

  1. Brain metastasis (if suspected, brain scan indicated)
  2. Previous chemotherapy for the currently existing metastatic disease
  3. Known or newly diagnosed diabetes
  4. Subjects with ACS within the last three months,
  5. Stage 3 or 4 heart failure defined according to the NYHA criteria
  6. Uncontrolled angina
  7. Contraindications to metformin (renal impairment [eGFR <45 mL/min/1.73m2], known hypersensitivity to metformin, acute illness [dehydration, severe infection, shock, acute cardiac failure]), and suspected tissue hypoxia
  8. Surgery (excluding diagnostic biopsy, central venous catheter) or irradiation within 2 weeks prior to study entry defined as given written informed consent
  9. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
  10. Administration of any investigational agent(s) within 4 weeks prior to study entry,
  11. Previous exposure to EGFR-pathway targeting therapy,
  12. Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
  13. Known grade 3 or 4 allergic reaction to any of the components of the treatment
  14. 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 ³ 5 years will be allowed to enter the trial)
  15. Pregnancy or lactation
  16. Inadequate contraception (male or female subjects) if of childbearing or procreative potential
  17. Known drug abuse/ alcohol abuse
  18. Legal incapacity or limited contractual capacity
  19. Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent