Randomized phase 3 trial comparing FOLFOX to gemcitabine in metastatic first-line in patients with pancreatic adenocarcinoma and non-fit for FOLFIRINOX (GEMFOX)

Prior treatment

• Treatment with any other investigational medicinal product within 28 days prior to study entry,
• Concomitant administration of live, attenuated virus vaccine and concomitant administration of prophylactic phenytoin.
• Patient receiving concomitant radiotherapy,
• Known dihydropyrimidine dehydrogenase (DPD) total or partial deficiency (controlled before inclusion by DPD genotypage or uracilemia dosage whatever the anteriority),
  • 9.Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),

Other illness

• History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
• Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
• Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,
• Known uncontrolled bacterial infection
• History or active interstitial lung disease (ILD),
• Patients with known allergy to active substance or any excipient of study drugs,
• Allergy to iodinated contrast product
• Local or locally advanced disease (stage I to III),
  • 20- Participation in another interventional research (medical treatment or medical device).

Lab values

• Poor nutritional status (albuminemia level ≤ 25 g/l)

Age

• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, iv/ malignancy with indolent evolution not requiring treatment,

Other

• Patients under legal protection or unable to consent
• Patient uses warfarin or other antivitamin k,
• Electrolytic report uncontrolled: hypercalcemia and/or hypokalemia and/or hypomagnesemia,
• Pre-existing permanent neuropathy (NCI grade ≥2),

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Adequate renal function: serum creatinine level <150μM and estimated creatinine clearance >30ml/min,
• Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
• Total bilirubin ≤3 x ULN,
• QT / QTc interval at baseline ECG (performed within 1 month before randomization) < than 450 msec for men and < than 470 msec for women,
• Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 28days prior to randomization,
• Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
• Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment
• Affiliation to a French social security system (recipient or assign).
• Histologically or cytologically proven adenocarcinoma of the pancreas,
• In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,
• Metastatic disease confirmed (stage IV),
• No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),
• Age ≥18 years,
• Patient non-fit for FOLFIRINOX with ECOG performance status (PS) 0-2,
• For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required,
• Haematological status: neutrophils (ANC) >2x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,