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

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

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

Study Overview

• Status: Completed
• Conditions: Carcinoma; Pancreatic Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Folinic Acid; Drug: 5-Fluoro-uracil; Drug: L-folinic

Detailed Description

Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aix-en-Provence, France, 13100
    • Centre Hospitalier Intercommunal Aix-Pertuis
  • Amiens, France
    • CHU Amiens - Hopital Nord
  • Angers, France
    • CHU d'Angers
  • Auxerre, France
    • Centre Hospitalier d'Auxerre
  • Avignon, France
    • Centre Hospitalier Henri Duffaut
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Bordeaux, France, 33077
    • Polyclinique Bordeaux Nord
  • Boulogne sur Mer, France, 62321
    • CH Boulogne sur Mer
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Caen, France, 14033
    • CHU côte de Nacre
  • Chambray-les-tours, France
    • Hopital Trousseau
  • Colmar, France
    • Hopitaux Civils de Colmar
  • Dijon, France
    • CH de Dijon
  • La Roche Sur Yon, France, 85925
    • CHD Vendée
  • Laon, France, 02000
    • Centre Hospitalier de Laon
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Limoges, France
    • CHU de Limoges
  • Lyon, France, 69437
    • Hopital Edouard Herriot - Lyon
  • Lyon, France
    • hôpital Saint Joseph Saint Luc
  • Marseille, France, 13003
    • Hôptal Européen
  • Marseille, France, 13365
    • Hopital de la Timone
  • Meaux, France, 77000
    • Centre Hospitalier de Meaux
  • Montivilliers, France
    • Groupe Hospitalier du Havre Jacques Monod
  • Nantes, France
    • Chu Hotel Dieu
  • Nice, France
    • Centre Antoine Lacassagne
  • Orléans, France
    • CHR d'Orléans La Source
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France
    • Groupe hospitalier Paris saint Joseph
  • Paris, France
    • Groupe Hospitalier Pitie Salpetriere
  • Pringy, France
    • Ch Annecy Genevois
  • Reims, France, 51092
    • CHU - Robert Debre
  • Rouen, France
    • CHU Rouen
  • Saint Brieuc, France, 22190
    • Hôpital Privé des Côtes d'Armor
  • Saint Herblain, France
    • Centre Regional Rene Gauducheau
  • Saint Malo, France, 35403
    • Centre Hospitalier de Saint Malo
  • Saint Priest En Jarez, France, 42271
    • Institut de Cancérologie Lucien Neuwirth
  • Saint-Aubin-lès-Elbeuf, France
    • CHI Elbeuf
  • Saint-Nazaire, France
    • Clinique Mutualiste de l'Estuaire
  • Saint-quentin, France
    • Hôpital privé Saint Claude
  • Soissons, France, 02209
    • Centre Hospitalier de Soissons
  • Strasbourg, France
    • Centre Paul Strass
  • Tarbes, France
    • Polyclinique de l'Ormeau-GROP
  • Toulouse, France, 31059
    • Centre Hospitalier de Rangueil
  • Villejuif, France
    • Gustave Roussy

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
3. 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)
4. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
5. WHO Performance status (PS) 0-1
6. Age ≥18 years

7. 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
8. Adequate vital functions
9. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.
10. Patient information and signed informed consent form
11. Public or private health insurance coverage
12. Uracilemia < 16 ng/ml

Exclusion Criteria:

1. 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
2. Patient with metastasis or with history of metastasis
3. 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)
4. Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
5. Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
6. Pregnant woman
7. Fructose intolerance
8. Patients currently treated by warfarin
9. Persons deprived of liberty or under guardianship
10. Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Gemcitabine; 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
Experimental: Arm B: Folfirinox; 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: Oxaliplatin; Drug: Irinotecan; Drug: Folinic Acid; Drug: 5-Fluoro-uracil; Drug: L-folinic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite index for treatment early severe toxicity	Biliary tract infection Grade 3-4 + any grade 5 toxicities + chemotherapy interruption for toxicity during the first four cycles.	First four chemotherapy cycles, 16 weeks
Adverse events (NCI-CTCAE version 4.0); observance of chemotherapy	Observance of chemotherapy	During treatment phase, 24 weeks
Overall Survival	The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether SRBT improves overall survival compared to standard of care.	Until death, assessed up 128 weeks after randomization
Progression-free survival: pattern of failure	The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.	Until Disease Progression, assessed uo until 128 weeks after randomization
Percentage of secondarily curative-intent surgery	Percentage of patients who will undergo an exeresis of their pancreatic tumor, with R0 resection confirmed by anatomopathic pathology.	Until surgery, if applicable, up until 128 weeks after randomization
Objective tumour response, disease control and their duration	Objective tumour response, disease control and their duration (RECIST version 1.1),	Until disease progression or date of death, assessed up until 128 weeks after randomization
Time to treatment failure	Time to treatment failure	From randomisation to the end of treatment
Quality of life questionnaire - Core 30 (QLQ-C30)	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	assessed up until 128 weeks after randomization

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Michel DUCREUX, Professor, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2015
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): September 25, 2023

Study Registration Dates

• First Submitted: August 3, 2015
• First Submitted That Met QC Criteria: August 31, 2015
• First Posted (Estimated): September 3, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: FOLFIRINOX; locally advanced pancreatic carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Carcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin; Folic Acid; Gemcitabine
• Other Study ID Numbers: PRODIGE 29 (UCGI 26); 2014-003510-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No