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

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ClinicalTrials.gov Identifier: NCT02352337
Recruitment Status : Active, not recruiting
First Posted : February 2, 2015
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: FOLFIRINOX Drug: LV5FU2 Drug: FOLFIRI.3 Drug: Gemcitabine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomised Phase II Study in Metastatic Pancreatic Cancer Evaluating FOLFIRINOX +/- LV5FU2 in Maintenance Versus Firgem in First-line
Actual Study Start Date : December 23, 2014
Actual Primary Completion Date : December 2017
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: FOLFIRINOX
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
Perfusion :oxaliplatine, Irinotecan ,folinic acid, 5FU bolus and continue

Experimental: FOLFIRINOX + LV5FU2 in maintenance

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
Perfusion :oxaliplatine, Irinotecan ,folinic acid, 5FU bolus and continue

Drug: LV5FU2
Perfusion: Folinic Acid,5FU Bolus,5FU continue

Experimental: FIRGEM

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
Perfusion :Irinotecan,Acide folinique ,5FU continue

Drug: Gemcitabine
Gemcitabine perfusion




Primary Outcome Measures :
  1. Rate of patients alive and without radiological and/or clinical progression [ Time Frame: 6 months after randomization ]
    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.


Secondary Outcome Measures :
  1. Duration of disease control [ Time Frame: After randomisation ]
  2. Toxicity (NCI-CTC V4.0) [ Time Frame: After randomisation ]
  3. Time to progression during the maintenance of treatment [ Time Frame: After randomization ]
  4. Overall survival [ Time Frame: 2 years ]
  5. Progression survival [ Time Frame: 2 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352337


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Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: DAHAN Laetitia, MD MARSEILLE La Timone

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT02352337     History of Changes
Other Study ID Numbers: PRODIGE35
First Posted: February 2, 2015    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Federation Francophone de Cancerologie Digestive:
cancer
pancreatic cancer
metastatic pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Fluorouracil
Irinotecan
Leucovorin
Levoleucovorin
Folic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Antidotes
Protective Agents
Vitamin B Complex