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

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: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: FOLFIRINOX; Drug: LV5FU2; Drug: FOLFIRI.3; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 2

Contacts and Locations

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
    • Hopital 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
    • Hôpitaux 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
    • Hôpital Privé 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 Eugène 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

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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

How is the study designed?

Design Details

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

Number of Arms

3

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
Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization.	Progression was defined as radiological progression according to RECIST v1.1 criteria and/or clinical progression according to the investigator. Progression or death (for any reason) was considered if the event occured within the first 6 months since randomization. 6 month scans were 6 month scans with a +/- 1 month window.	6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of last news was taken into account. The analysis was done on the ITT population meaning the patients who have been randomized. Numbers of patients correspond the number of patients randomized in the study.	Up to 3 years after the treatment start
Progression-free Survival (PFS)	It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) and/or clinical progression according to the investigator or death (whatever the cause is); Patients alive without progression were censored at date of last news .	up to 12 months after randomization

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Investigators: Principal Investigator: DAHAN Laetitia, MD, MARSEILLE La Timone

Publications and helpful links

General Publications

• Dahan L, Williet N, Le Malicot K, Phelip JM, Desrame J, Bouche O, Petorin C, Malka D, Rebischung C, Aparicio T, Lecaille C, Rinaldi Y, Turpin A, Bignon AL, Bachet JB, Seitz JF, Lepage C, Francois E; PRODIGE 35 Investigators/Collaborators. Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial. J Clin Oncol. 2021 Oct 10;39(29):3242-3250. doi: 10.1200/JCO.20.03329. Epub 2021 Jul 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2015
• 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 (Estimated): February 2, 2015

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: cancer; pancreatic cancer; metastatic pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folfirinox; Gemcitabine
• Other Study ID Numbers: PRODIGE35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED