Metformin Combined With Chemotherapy for Pancreatic Cancer (GEM)
Locally Advanced Pancreatic Cancer, Metastatic Pancreatic Cancer
About this trial
This is an interventional treatment trial for Locally Advanced Pancreatic Cancer focused on measuring pancreatic cancer, metformin, MAPK pathway, PI3K/Akt pathway, gemcitabine
Eligibility Criteria
Inclusion Criteria:
- Signed informed content obtained prior to treatment
- Cytological or histological confirmed carcinoma of the pancreas
- Metastatic cancer
- Measurable lesion according to RECIST criteria
- ECOG/ WHO performance 0-2
- Age > 18 years
- Adequate renal function (creatinine < 150 µmol/L and/ or a creatinine clearance > 60 ml/ L)
- Adequate liver function (bilirubin < 1.5 times upper limit of normal, ALAT or ASAT < 5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit of normal in absence of liver metastases).
- Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)
- Mentally, physically, and geographically able to undergo treatment and follow up
Exclusion Criteria:
- Clinical or radiological evidence of CNS metastases
- Pregnancy (positive serum pregnancy test) and lactation
- Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
Patients who have any severe and/or uncontrolled medical conditions:
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to randomization, serious uncontrolled cardiac arrhythmia
- uncontrolled diabetes as defined by fasting serum glucose >2X ULN.
- active or uncontrolled severe infection.
- cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- severely impaired lung function
- Previous treatment with erlotinib
- Previous treatment with gemcitabine for metastatic disease
- Previous treatment with gemcitabine combined with radiotherapy for locally advanced pancreatic cancer within 6 months prior to study entry
- Patients with a known hypersensitivity to metformin
- Use of metformin in the previous 6 months
Sites / Locations
- Academic Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Gemcitabine, erlotinib and metformin
Gemcitabine, erlotinib and placebo
Gemcitabine at a dose of 1000 mg/m2 (iv, 30 minutes) will be given weekly, for 3 weeks, followed by one week without gemcitabine. Erlotinib will be administered at a daily dose of 100 mg at least one hour before or 2 hours after the ingestion of food. Metformin will be administered at a dose of 500 mg twice daily. If well tolerated the dose will be increased to 1000 mg twice daily in the second week.
Gemcitabine at a dose of 1000 mg/m2 (iv, 30 minutes) will be given weekly, for 3 weeks, followed by one week without gemcitabine. Erlotinib will be administered at a daily dose of 100 mg at least one hour before or 2 hours after the ingestion of food. PLacebo will be administered at a dose of 500 mg twice daily. If well tolerated the dose will be increased to 1000 mg twice daily in the second week.