Randomized Multicenter Phase II/III Study With Adjuvant Gemcitabine Versus Neoadjuvant / Adjuvant FOLFIRINOX for Resectable Pancreas Carcinoma

Study Overview
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Brief Summary
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In this multicenter study, patients with resectable pancreatic carcinoma will be treated with (a) surgery followed by 6 cycles gemcitabine or (b) 4-6 cycles FOLFIRINOX followed by surgery followed by 4-6 cycles FOLFIRINOX. The overall survival between both therapies will be compared as well as other parameters.

Detailed Description
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This is a phase II/III randomized multicenter study. Patients with resectable pancreatic carcinoma will be randomized in Arm A (surgery plus adjuvant gemcitabine, 6 cycles) or Arm B (4-6 cycles FOLFIRINOX neoadjuvant, 4-6 cycles FOLFIRINOX adjuvant). Primary endpoint is the overall survival, secondary endpoints are progression-free survival, perioperative morbidity and mortality, rate of R0 resections, tolerability and feasibility of neoadjuvant FOLFIRINOX and others.

Official Title
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Randomized Multicenter Phase II/III Study With Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer

Conditions
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Resectable Prancreas Carcinoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Oxaliplatin
* Drug: 5-Fluorouracil
* Drug: Irinotecan
* Drug: Natriumfolinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the pankreas. For histological confirmation, max. 3 tests are allowed. If no confirmation of carcinoma is possible, the patient can not be included into the study. Radiological confirmation of a locally limited curativ resectable (primarily resectale or borderline situation) pankreas carcinoma without distant metastases. no prior pancreas resection no prior cytostatic chemotherapy female and male patients > 18 and <=75 years using contraception ECOG ≤ 1 medical resectability granulocytes > 1.500/µl thrombocytes > 100.000/µl hemoglobin ≥ 8,0 g/dl serumcreatinine ≤ 1.5x of normal value or Creatinine-Clearance > 50 ml/min written informed consent Exclusion Criteria: Endocrine pancreas carcinoma locally advanced inoperable stages: non-resectable infiltration of V. porta or longway infiltration of A. mesenterica superior or infiltration of Truncus coeliacus. distant metastases Relapse prior radiotherapy of measurable lesions peritonealcarcinosis malignant secondary disease, dated back < 5 years (exeption: in-situ-carcinoma of the cervix, adequately treated skin basal cell carcinoma) contraindication for operative resection ECOG ≥ 2 severe liver dysfunction (AST/ALT>3,5xULN, AP>6xULN) Transhepatic drainage active CHD (symptoms present), cardiomyopathy or heart insufficiency stage III-IV according to NYHA and EF < 45% severe non-surgical accompanying diseases or acute infection chronic diarrhea chronic inflammable gastro-intestinal disease peripheral polyneuropathy > NCI grade II pregnancy or lactation hypersensibility or contraindication for Gemcitabine, Oxaliplatin, Natriumfolinate, Irinotecan or 5-Fluorouracil participation in another interventional trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFIRINOX<br>Oxaliplatin 85mg/m², Irinotecan 180mg/m², 5-FU 400mg/m² Bolus i.v., 5-FU continuous Infusion 2400 mg/m² Natriumfolinate 400mg/m² 46h d1; qd15 6 cycles pre- and 6 cycles post- surgery | Drug: Oxaliplatin<br> <br> Drug: 5-Fluorouracil<br> <br> Drug: Irinotecan<br> <br> Drug: Natriumfolinate<br> <br> |
| Active Comparator: Gemcitabine<br>Gemcitabine 1000 mg/m² d1, d8, d15; qd 29; 6 cycles after surgery | Drug: Gemcitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median overall survival |  | From date of randomization until the date of death from any cause assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median progression-free survival (PFS) |  | From date of randomization until the date of first documented progression / relapse or date of death from any cause, whichever came first, assessed up to 24 months | 
| perioperative morbidity and mortality |  | 30 days after surgery | 
| R0 resection rate |  | 2 months after surgery | 
| pathological complete remission | during surgery, paraffin embedded tissue is prepared for analysis which is analyzed for remission grading at the central pathology afterwards | at surgery | 
| adverse events (grade, number per patient) related to of G-CSF prophylaxis in the Folfirinox arm |  | up to 40 weeks | 
| prevalence of iron deficiency |  | baseline, d1 of every cycle, end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas cancer, neoadjuvant chemotherapy, Folfirinox, gemcitabine