First-line Metastatic Pancreatic Cancer : FOLFIRINOX +/- LV5FU2 in Maintenance Versus Firgem

Study Overview
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Brief Summary
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The pancreas cancer is the 4th cause of death. All stage confused, the survival at 5 years is note over 5 %. At metastatic stage, the pancreatic adenocarcinoma is an incurable disease with the survival median of 2-4 months without chemotherapy. Up to 2011, gemcitabine was the only reference treatment of this type of cancer. But until, the FOLFIRINOX could permitted to improve significantly the overall survival (6,8 months with gemcitabine vs 11,1 months with FOLFIRINOX) and the progression free survival (3,3 months with gemcitabine vs 6,4 months with FOLFIRINOX) for patients under 76 years. Main toxicities of this treatment are hematological, gastrointestinal and neuropathy with apparition of sensitive neuropathy, reversible, related to oxaliplatin. These results are on a population under 76 years old. In this study, the median age of patients at inclusion was 61 years old and FOLFIRINOX was still beneficial for patients more than 65 years old. Given the increase of proportion of patients than more of 65 years old with pancreatic cancer and given the increase of life expected, it is important to know the effectiveness and tolerance of such treatment for patient older than 65 years and 76 years. FIRGEM is an original strategic sequential treatment witch alternates, every 2 month, 4 cycles of FOLFIRI.3 and 2 cycles of 3 injections of gemcitabine. There is no cross resistance known between this 2 treatments witch limit toxicities and preserve quality of life of patients. A Phase II trial testing this treatment regimen to classical regimen of gemecitabine, showed an overall survival of 11 months in the FIRGEM regimen and an overall survival of 8,2 months in the gemcitabine regimen. The rate of progression was 45% near of progression rate with FOLFIRINOX. Tolerance is close to that FOLFIRINOX regimen but this strategic doesn't induce limiting neurotoxicities and allow to use oxaliplatin in 2de line of treatment. The trial propose to evaluate the effectiveness and tolerance of FOLFIRINOX regimen (8 cycles) with LV5FU2 in maintenance (that could increase the FOLFIRINOX tolerable without decrease efficiency), to FIRGEM regimen and to FOLFIRINOX (12 cycles) which is the reference regimen.

Official Title
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Randomised Phase II Study in Metastatic Pancreatic Cancer Evaluating FOLFIRINOX +/- LV5FU2 in Maintenance Versus Firgem in First-line

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: FOLFIRINOX
* Drug: LV5FU2
* Drug: FOLFIRI.3
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic disease At least one mesurable lesion according to RECIST V1.1 criteria No prior chemotherapy (excepted if there is at least on lestion out of the irradition area) Age > 18 years. A favorable adviced by an onco geriatrician would be mandatory for inclusion of patients older than 75 older Performance statut (WHO) 0-1 Polynyclear ≥ 1500/mm3 Bilirubine ≤ 1,5 fois la LSN, creatinin < 120μmol / L Signed informed consent form Exclusion Criteria: Another type of pancreas tumor, as endocrine tumor ou with acinous cells Ampulloma Cerebral or meningeal metastasis Gilbert disease Neuropathie > or = grade 1 Study treatments contraindication Uncontrolled diarrhoea or inflamatory disease of colon or rectum, or bowel obstruction or bowel sub-obstruction no resolved with specific treatment Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease prevent patient to receive study Cancer within the 5 years before inclusion, except for int situ cancer of the neck of the uterus or basal cell skin cancer Significant previous cardiac and respiratory disease Patient included in an other therapeutic study with experimental treatment Pregnancy or breast feeding Patient depreved of freedom or under gardianship Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: FOLFIRINOX<br>Every two weeks (maximum of 12 cycles) : Oxaliplatin 85 mg / m2 Day1 in 2 hours - then Irinotecan 180 mg / m2 Day1 in 90 minutes - Folinic acid 400 mg / m2 Day1 in 2 h (during the irinotecan infusion) - 5-FU bolus 400 mg / m² Day1 followed by continuous 5-FU 2400 mg / m2 total over 46 hours | Drug: FOLFIRINOX<br>* Perfusion :oxaliplatine, Irinotecan ,folinic acid, 5FU bolus and continue<br>|
| Experimental: FOLFIRINOX + LV5FU2 in maintenance<br>Folfirinox during 4 months followed by LV5FU2 maintenance until progression: Folfirinox (as described in arm FOLFIRINOX) LV5FU2 : Folinic acid 400 mg/m² (200 mg/m² if Elvorine), in perfusion over 2 hours the 5FU 400 mg/m² in bolus over 10 mn followed by 5FU 2400 mg/m² in perfusion over 46 hours. | Drug: FOLFIRINOX<br>* Perfusion :oxaliplatine, Irinotecan ,folinic acid, 5FU bolus and continue<br>Drug: LV5FU2<br>* Perfusion: Folinic Acid,5FU Bolus,5FU continue<br>|
| Experimental: FIRGEM<br>Alternance of 2 months of FOLFIRI.3 with 2 months of GEMCITABINE: Folfiri.3: Irinotécan 90 mg/m² at day 1 in perfusion over 60 minutes in parralel of folinic acid Folinic acid 400 mg/m² (or 200 mg/m² Elvorine) at day 1 in perfusion over 2 hours 5FU continue 2000 mg/m² over 46 heures then irinotécan at 90 mg/m² (1h) at day 3 when 5U perfusion is over Gemcitabine: 1000 mg/m² in perfusion over 30 mn at day 1,8,15,29,36 and 43 over (1 injection per week during 3 weeks followed with 7 days of rest ) | Drug: FOLFIRI.3<br>* Perfusion :Irinotecan,Acide folinique ,5FU continue<br>Drug: Gemcitabine<br>* Gemcitabine perfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients alive and without radiological and/or clinical progression | Progression is defined as radiological (RECIST v1.1) and/or clinical according to the investigator. Progression or death (whatever the reason is) will be taking into account if the event occurs during the 6 first months of treatment. | 6 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression during the maintenance of treatment |  | After randomization | 
| Overall survival |  | 2 years | 
| Progression survival |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, pancreatic cancer, metastatic pancreatic cancer