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

NCT ID: NCT02352337

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-12
• Study Completion Date: 2021-08-31

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.

Conditions

Metastatic Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

FOLFIRINOX

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

FOLFIRINOX

Intervention Type: DRUG

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

LV5FU2

Intervention Type: DRUG

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

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 )

Group Type: EXPERIMENTAL

FOLFIRI.3

Intervention Type: DRUG

Perfusion :Irinotecan,Acide folinique ,5FU continue

Gemcitabine

Intervention Type: DRUG

Gemcitabine perfusion

Interventions

FOLFIRINOX

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

Intervention Type: DRUG

LV5FU2

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

Intervention Type: DRUG

FOLFIRI.3

Perfusion :Irinotecan,Acide folinique ,5FU continue

Intervention Type: DRUG

Gemcitabine

Gemcitabine perfusion

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

DAHAN Laetitia, MD

Role: PRINCIPAL_INVESTIGATOR

MARSEILLE La Timone

Locations

CHU - Hôtel Dieu

Angers, , France

CH

Auxerre, , France

CH - Henri Duffaut

Avignon, , France

Centre d'oncologie et de radiothérapie

Bayonne, , France

CH

Bayonne, , France

Ch - Ch Beauvais

Beauvais, , France

CHU

Besançon, , France

Bezier Ch

Béziers, , France

Hôpital Avicenne

Bobigny, , France

Polyclinique Bordeaux Nord

Bordeaux, , France

CH -Duchenne

Boulogne-sur-Mer, , France

CHU Côte de Nacre

Caen, , France

CHU Estaing

Clermont-Ferrand, , France

Hôpitaux Civils de Colmar

Colmar, , France

CH Compiègne-Noyon

Compiègne, , France

CHG

Corbeil-Essonnes, , France

CHU - Hôpital François Mitterand

Dijon, , France

CH

Dunkirk, , France

CHU de Grenoble

Grenoble, , France

Institut Daniel Hollard / Groupe Hospitalier Mutualiste

Grenoble, , France

Clinique Sainte Marguerite

Hyères, , France

CH Marne La Vallée Jossigny

Jossigny, , France

CHD

La Roche-sur-Yon, , France

CHU - Claude Huriez

Lille, , France

Hôpital du Scorff

Lorient, , France

CHU - Hôpital Edouard Herriot

Lyon, , France

Clinique de la Sauvegarde

Lyon, , France

Hôpital de la Croix Rousse

Lyon, , France

Hôpital Privé Jean Mermoz

Lyon, , France

La Timone

Marseille, , France

Hôpital Européen de Marseille

Marseille, , France

Hôpital privé

Marseille, , France

CH - Centre Hospitalier de Meaux

Meaux, , France

Centre Antoine Lassagne

Nice, , France

Hôpital de la Source -service HGE et cancérologie digestive

Orléans, , France

Hôpital de la Source- service d'oncologie

Orléans, , France

CHU AP - HP - Hôpital Européen Georges Pompidou

Paris, , France

Groupe Hospitalier Saint Joseph

Paris, , France

Hôpital La Pitié Salpetière

Paris, , France

CH Pau

Pau, , France

Centre Hospitalier Annecy Genevois

Pringy, , France

CHU Robert Debré

Reims, , France

Centre Eugène Marquis

Rennes, , France

CHU - Charles Nicolle

Rouen, , France

CHU

Saint-Etienne, , France

CH

Soissons, , France

CH

St-Malo, , France

Centre Paul Strauss

Strasbourg, , France

Clinique Sainte Anne

Strasbourg, , France

CH - Bigorra

Tarbes, , France

Hôpityal Trousseau

Tours, , France

CH

Valenciennes, , France

Institut Gustave Roussy

Villejuif, , France

Hôpital Privé de Villeneuve d'Ascq

Villeneuve-d'Ascq, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 34288696 (View on PubMed)

Boisteau E, Dahan L, Williet N, Le Malicot K, Desrame J, Bouche O, Petorin C, Malka D, Rebischung C, Aparicio T, Lecaille C, Rinaldi Y, Turpin A, Bignon AL, Bachet JB, Lepage C, Granger V, Legoux JL, Deplanque G, Baconnier M, Lecomte T, Bonnet I, Seitz JF, Francois E, Lievre A; PRODIGE 35 Investigator/Collaborators. Clinico-biological factors predicting the benefit of the LV5FU2 maintenance strategy as a first-line therapy in patients with metastatic pancreatic cancer. Oncologist. 2024 Sep 6;29(9):e1149-e1158. doi: 10.1093/oncolo/oyae079.

Reference Type: DERIVED

PMID: 39235326 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PRODIGE35

Identifier Type: -

Identifier Source: org_study_id