A Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma

NCT02539537 | Completed Phase 3 DMC

• 2 other identifiers: PRODIGE 29 (UCGI 26)2014-003510-82
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 45

Brief Summary

French national multicentric phase III trial evaluating chemotherapy with Folfirinox or gemcitabine in locally advanced pancreatic carcinoma.

Conditions

Pancreatic Cancer; Carcinoma

Keywords

locally advanced pancreatic carcinoma; FOLFIRINOX

Outcome Measures

Primary Outcomes (1)

• Progression-Free-Survival (PFS)

  To compare Progression-Free-Survival (PFS) between the two treatment arms

  From randomization until disease progression or date of death, assessed up until to 128 weeks

Secondary Outcomes (8)

• Composite index for treatment early severe toxicity

  First four chemotherapy cycles, 16 weeks

• Adverse events (NCI-CTCAE version 4.0); observance of chemotherapy

  During treatment phase, 24 weeks

• Overall Survival

  Until death, assessed up 128 weeks after randomization

• Progression-free survival: pattern of failure

  Until Disease Progression, assessed uo until 128 weeks after randomization

• Percentage of secondarily curative-intent surgery

  Until surgery, if applicable, up until 128 weeks after randomization

Study Arms (2)

Arm A: Gemcitabine

ACTIVE COMPARATOR

Gemcitabine 1000 mg/m² IV infusion over 30 minutes on D1 of each week for the 4 weeks of the first cycle (1 cycle = 4 weeks). For the following five cycles, gemcitabine infusion on D1, D8, and D15 of each cycle, followed by 1 week without injection (i.e. in total 4 cycles over 24 weeks; with 19 administrations of Gemcitabine).

Drug: Gemcitabine

Arm B: Folfirinox

EXPERIMENTAL

Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion. 5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days. Treatment will be continued for 24 weeks (12 cycles).

Drug: Folinic Acid; Drug: 5-Fluoro-uracil; Drug: Oxaliplatin; Drug: Irinotecan; Drug: L-folinic

Interventions

Gemcitabine DRUG

Arm A: Gemcitabine

Folinic Acid DRUG

Arm B: Folfirinox

5-Fluoro-uracil DRUG

Arm B: Folfirinox

Oxaliplatin DRUG

Arm B: Folfirinox

Irinotecan DRUG

Arm B: Folfirinox

L-folinic DRUG

Arm B: Folfirinox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
• Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or \> 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)
• Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
• WHO Performance status (PS) 0-1
• Age ≥18 years
• Patient with organ function as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
• Hemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 75 x 10⁹/L
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN
• Creatinine ≤ 2 x ULN
• Albumin \> 0.75 x lower limit of normal (LLN)
• Urea ≤ 2 x ULN

You may not qualify if:

• Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
• Patient with metastasis or with history of metastasis
• Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
• Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
• Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 \* 28 / \* 28
• Pregnant woman
• Fructose intolerance
• Patients currently treated by warfarin
• Persons deprived of liberty or under guardianship
• Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (45)

Centre Hospitalier Intercommunal Aix-Pertuis

Aix-en-Provence, 13100, France

Location

CHU Amiens - Hôpital Nord

Amiens, France

Location

CHU d'Angers

Angers, France

Location

Centre hospitalier d'Auxerre

Auxerre, France

Location

Centre hospitalier Henri Duffaut

Avignon, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord

Bordeaux, 33077, France

Location

CH Boulogne sur Mer

Boulogne-sur-Mer, 62321, France

Location

CHU Côte de Nacre

Caen, 14033, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Hôpital Trousseau

Chambray-lès-Tours, France

Location

Hôpitaux civils de Colmar

Colmar, France

Location

CH de Dijon

Dijon, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier de Laon

Laon, 02000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

CHU de Limoges

Limoges, France

Location

Hôpital Edouard Herriot - Lyon

Lyon, 69437, France

Location

Hôpital Saint Joseph Saint Luc

Lyon, France

Location

Hôptal Européen

Marseille, 13003, France

Location

Hôpital De La Timone

Marseille, 13365, France

Location

Centre Hospitalier de Meaux

Meaux, 77000, France

Location

Groupe Hospitalier du Havre Jacques Monod

Montivilliers, France

Location

CHU Hotel Dieu

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CHR d'Orléans La Source

Orléans, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Groupe hospitalier Paris Saint Joseph

Paris, France

Location

Groupe hospitalier Pitié Salpétrière

Paris, France

Location

CH Annecy Genevois

Pringy, France

Location

CHU - Robert Debre

Reims, 51092, France

Location

CHU Rouen

Rouen, France

Location

CHI Elbeuf

Saint-Aubin-lès-Elbeuf, France

Location

Hôpital Privé des Côtes d'Armor

Saint-Brieuc, 22190, France

Location

Centre Regional René Gauducheau

Saint-Herblain, France

Location

Clinique mutualiste de l'Estuaire

Saint-Nazaire, France

Location

Institut de cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42271, France

Location

Hôpital privé Saint Claude

Saint-Quentin, France

Location

Centre Hospitalier de Soissons

Soissons, 02209, France

Location

Centre Hospitalier de Saint Malo

St-Malo, 35403, France

Location

Centre Paul Strass

Strasbourg, France

Location

Polyclinique de l'Ormeau-GROP

Tarbes, France

Location

Centre Hospitalier de Rangueil

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Ducreux M, Desgrippes R, Rinaldi Y, Di Fiore F, Guimbaud R, Evesque L, Bachet JB, Vanelslander P, Lecomte T, Capitain O, Parzy A, Bolliet M, Etienne PL, Forestier J, El Hajbi F, Bignon AL, Lebrun-Ly V, De Sousa Carvalho N, Texier M, Bouche O. PRODIGE 29-UCGI 26 (NEOPAN): A Phase III Randomized Trial Comparing Chemotherapy With FOLFIRINOX or Gemcitabine in Locally Advanced Pancreatic Carcinoma. J Clin Oncol. 2025 Jul 10;43(20):2255-2264. doi: 10.1200/JCO-24-02210. Epub 2025 May 16.

  PMID: 40378359 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma

Interventions

Gemcitabine; Leucovorin; Oxaliplatin; Irinotecan

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids

Study Officials

• Michel DUCREUX, Professor

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: September 3, 2015
• Study Start: October 23, 2015
• Primary Completion: February 1, 2022
• Study Completion: September 25, 2023
• Last Updated: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (45)