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

August 18, 2022 updated by: Federation Francophone de Cancerologie Digestive

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

276

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
        • CHU - Hôtel Dieu
      • Auxerre, France
        • CH
      • Avignon, France
        • CH - Henri Duffaut
      • Bayonne, France
        • Centre d'oncologie et de radiothérapie
      • Bayonne, France
        • CH
      • Beauvais, France
        • Ch - Ch Beauvais
      • Besançon, France
        • CHU
      • Bobigny, France
        • Hôpital Avicenne
      • Bordeaux, France
        • Polyclinique Bordeaux Nord
      • Boulogne-sur-Mer, France
        • CH -Duchenne
      • Béziers, France, 34525
        • Bezier Ch
      • Caen, France
        • CHU côte de Nacre
      • Clermont Ferrand, France
        • CHU Estaing
      • Colmar, France
        • Hopitaux Civils de Colmar
      • Compiègne, France
        • CH Compiègne-Noyon
      • Corbeil-Essonnes, France
        • CHG
      • Dijon, France
        • CHU - Hôpital François Mitterand
      • Dunkerque, France
        • CH
      • Grenoble, France
        • Chu de Grenoble
      • Grenoble, France
        • Institut Daniel Hollard / Groupe Hospitalier Mutualiste
      • Hyeres, France
        • Clinique Sainte Marguerite
      • Jossigny, France
        • CH Marne La Vallée Jossigny
      • La Roche Sur Yon, France
        • CHD
      • Lille, France
        • CHU - Claude Huriez
      • Lorient, France
        • Hôpital du Scorff
      • Lyon, France
        • Hopital de La Croix Rousse
      • Lyon, France
        • Hopital Prive Jean Mermoz
      • Lyon, France
        • Clinique de la Sauvegarde
      • Lyon, France
        • Chu - Hôpital Edouard Herriot
      • Marseille, France, 13000
        • La Timone
      • Marseille, France
        • Hôpital Européen de Marseille
      • Marseille, France
        • Hôpital privé
      • Meaux, France
        • CH - Centre Hospitalier de Meaux
      • Nice, France
        • Centre Antoine Lassagne
      • Orléans, France
        • Hôpital de la Source -service HGE et cancérologie digestive
      • Orléans, France
        • Hôpital de la Source- service d'oncologie
      • Paris, France
        • CHU AP - HP - Hôpital Européen Georges Pompidou
      • Paris, France
        • Groupe Hospitalier Saint Joseph
      • Paris, France
        • Hôpital La Pitié Salpetière
      • Pau, France
        • CH Pau
      • Pringy, France
        • Centre Hospitalier Annecy Genevois
      • Reims, France
        • CHU Robert Debré
      • Rennes, France
        • Centre Eugene Marquis
      • Rouen, France
        • CHU - Charles Nicolle
      • Saint-Etienne, France
        • CHU
      • Saint-Malo, France
        • CH
      • Soissons, France
        • CH
      • Strasbourg, France
        • Centre Paul Strauss
      • Strasbourg, France
        • Clinique Sainte Anne
      • Tarbes, France
        • CH - Bigorra
      • Tours, France
        • Hôpityal Trousseau
      • Valenciennes, France
        • CH
      • Villejuif, France
        • Institut Gustave Roussy
      • Villeneuve D'Ascq, France
        • Hopital Prive de Villeneuve d'Ascq

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months after randomization

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Investigators

  • Principal Investigator: DAHAN Laetitia, MD, MARSEILLE La Timone

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 23, 2014

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

January 28, 2015

First Posted (Estimate)

February 2, 2015

Study Record Updates

Last Update Posted (Actual)

August 22, 2022

Last Update Submitted That Met QC Criteria

August 18, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRODIGE35

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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