Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma

NCT ID: NCT01526135

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-16
• Study Completion Date: 2021-07-16

Brief Summary

This is a multicentric randomized phase III trial comparing adjuvant chemotherapy with gemcitabine versus 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (mFolfirinox) in patients with resected pancreatic adenocarcinoma.

Detailed Description

STUDY DESIGN/ Evaluation criteria Main criterion: efficacy The main criterion is the disease-free survival at 3 years. Disease-free survival is the time delay between the date of randomization and the date at which the 1st cancer-related event such as local relapse, distant metastasis, a second cancer or death from any cause is observed. Patients without event at the time of anlaysis will be censored at the date of last follow-up visit.

Locoregional relapse is a disease relapse occurring at the site of primary resection, in the pancreas or in the associated regional lymph nodes.

Metastatic relapse is the distant disease recurrence involving any possible sites of relapse (peritoneal, hepatic, pulmonary, and distant lymph nodes).

Secondary criteria Overall and specific survival Overall survival is the time delay between the date of randomization and the patient's death, irrespective of its cause. Patients who are still living at the time of analysis will be censored at the date of last follow-up visit.

Specific survival is the time delay between the date of randomization and the patient's death due to the treated cancer or a treatment-related complication.

Metastasis-free survival Metastasis-free survival is the time delay between the date of randomization and the date of the 1st distant event occurrence (peritoneal, hepatic, pulmonary, and lymph nodes). Loco-regional events will be discarded and patients still living without metastasis at the time of analysis will be censored at the date of last follow-up examination objectively assessing this type of event.

Tolerance Patients evaluable for toxicity must have received at least one course or injection of the treatment.

Conditions

Pancreatic Adenocarcinoma (Ductal Adenocarcinoma)

Study Design

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

Study Groups

Arm A GEMCITABINE

Arm A : Gemcitabine 1000 mg/m² IV infusion over 30 minutes, weekly, during 3 weeks + 1 week of rest (= 1 cycle) repeated 6 times (i.e., 6 cycles) during 24 weeks

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m² IV infusion over 30 minutes, weekly, during 3 weeks + 1 week of rest (= 1 cycle) repeated 6 times (i.e., 6 cycles) during 24 weeks

Arm B mFOLFIRINOX

Arm B : mFOLFIRINOX every 14 days, 12 cycles, 24 weeks. Oxaliplatin (Eloxatin®) 85 mg/m² D1 over 2 hours, followed by Irinotecan (Campto®) 150 mg/m² D1 over 90 minutes to begin 30 min. after the Folinic acid infusion is started.

Folinic acid 400 mg/m² (racemic mixture) (or 200 mg/m² if L-folinic acid is used), IV infusion over 2 hours.

5-FU 2.4 g/m² IV continuous infusion over 46 hours (1200 mg/m²/ day)

Group Type: EXPERIMENTAL

mFolfirinox

Intervention Type: DRUG

mFolfirinox every 14 days, 12 cycles, 24 weeks.

mFolfirinox : Oxaliplatin (Eloxatin®) 85 mg/m² D1 over 2 hours, followed by Irinotecan (Campto®) 150 mg/m² D1 over 90 minutes to begin 30 min. after the Folinic acid infusion is started.

Folinic acid 400 mg/m² (racemic mixture) (or 200 mg/m² if L-folinic acid is used), IV infusion over 2 hours.

5-FU 2.4 g/m² IV continuous infusion over 46 hours (1200 mg/m²/ day)

Interventions

mFolfirinox

mFolfirinox every 14 days, 12 cycles, 24 weeks.

mFolfirinox : Oxaliplatin (Eloxatin®) 85 mg/m² D1 over 2 hours, followed by Irinotecan (Campto®) 150 mg/m² D1 over 90 minutes to begin 30 min. after the Folinic acid infusion is started.

Folinic acid 400 mg/m² (racemic mixture) (or 200 mg/m² if L-folinic acid is used), IV infusion over 2 hours.

5-FU 2.4 g/m² IV continuous infusion over 46 hours (1200 mg/m²/ day)

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m² IV infusion over 30 minutes, weekly, during 3 weeks + 1 week of rest (= 1 cycle) repeated 6 times (i.e., 6 cycles) during 24 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically proven pancreatic ductal adenocarcinoma. Intraductal papillary mucinous tumor of the pancreas (IPMT) with invasive components are eligible.

2. Macroscopically complete resection (R0 or R1 resection).

3. Patients aged from 18 to 79 years.

4. WHO performance status 0-1.

5. No prior radiotherapy and no previous chemotherapy.

6. Full recovery from surgery and patient able to receive chemotherapy: adequate oral nutrition of ≥1500 calories per day and free of significant nausea and vomiting.

7. Adequate hematologic function (Absolute neutrophil count ANC ≥1,500 cells/mm³, platelets ≥100 000 cells/mm³ and hemoglobin ≥10 g/L - possibly after transfusion -).

8. Serum total bilirubin ≤1.5 times the institutional upper limit of normal.

9. Creatinine level <130 micromol/L (14.7 mg/L).

10. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men.

11. Interval since surgery between 21 and 84 days.

12. Patient information and signed informed consent.

13. Public or private health insurance coverage.

Exclusion Criteria

1. Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and malignant ampulloma.

2. Metastases (including ascites or malignant pleural effusion).

3. Macroscopic incomplete tumor removal (R2 resection).

4. CA 19-9 > 180 U/ml within 21 days of registration on study.

5. No heart failure or coronary heart disease symptoms.

6. No major comorbidity that may preclude the delivery of treatment or active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes.

7. Pre-existing neuropathy, Gilbert's disease or genotype UGT1A1 * 28 / * 28.

8. Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine or severe postoperative uncontrolled diarrhea.

9. Concomitant occurrence of another cancer, or history of cancer except in situ carcinoma of the cervix treated or basal cell carcinoma or squamous cell carcinoma.

10. Fructose intolerance.

11. Persons deprived of liberty or under guardianship.

12. Psychological, familial, sociological or geographical condition potentially. hampering compliance with the study protocol and follow-up schedule.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Cancer Trials Group

NETWORK

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry CONROY, PROF

Role: PRINCIPAL_INVESTIGATOR

Centre Alexis Vautrin-VANDOEUVRE LES NANCY

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

CancerCare Manitoba, St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Dr Leon Richard Oncology Centre

Moncton, New Brunswick, Canada

The Royal Victoria Hospital - Cancer Care Program

Barrie, Ontario, Canada

Department of Medical Oncology Health Sciences North

Greater Sudbury, Ontario, Canada

Juravinski Cancer centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Ottawa Health Research Institute

Ottawa, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

General Surgery - TGH Site, Univ. Health Network

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University (Department of Oncology)

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allain Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre, University of Saskatchewan

Saskatoon, Saskatchewan, Canada

The Moncton Hospital

Moncton, , Canada

CHUQ - Hotel-Dieu de Quebec

Québec, , Canada

Algoma District Cancer Program, Sault Area Hospital

Sault Ste. Marie, , Canada

CHU Nord

Amiens, , France

ICO Paul Papin

Angers, , France

Hôpital Avicenne

Bobigny, , France

Institut Bergonié

Bordeaux, , France

CHU Côte de Nacre

Caen, , France

Hôpital Beaujon

Clichy, , France

Hôpital Louis Pasteur

Colmar, , France

CHU de Dijon - Site Bocage

Dijon, , France

CHD Vendée

La Roche-sur-Yon, , France

Hôpital Huriez

Lille, , France

Centre Léon Bérard

Lyon, , France

Hôpital de la Croix-Rousse

Lyon, , France

Hôpital Privé Jean Mermoz

Lyon, , France

CHU Nord

Marseille, , France

CHU Timone Adulte

Marseille, , France

Fondation Ambroise Paré / Hôpital Européen

Marseille, , France

Institut Paoli Calmettes

Marseille, , France

CH Layné

Mont-de-Marsan, , France

CHU De ST Eloi

Montpellier, , France

CRCL Val d'Aurelle

Montpellier, , France

Centre Antoine-Lacassagne

Nice, , France

CHR Orléans - La Source

Orléans, , France

Groupe Hospitalier Paris Saint Joseph

Paris, , France

Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Hôpital Saint-Jean

Perpignan, , France

Hôpital Haut-Lévêque

Pessac, , France

Centre hospitalier de Reims

Reims, , France

CHU Rouen

Rouen, , France

Centre René Gauducheau

Saint-Herblain, , France

Centre Paul Strauss

Strasbourg, , France

Hôpital Trousseau

Tours, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Hôpital de Brabois-CHU de Nancy

Vandœuvre-lès-Nancy, , France

Countries

Canada; France

References

Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, Mitry E, Biagi JJ, Evesque L, Artru P, Lecomte T, Assenat E, Bauguion L, Ychou M, Bouche O, Monard L, Lambert A, Hammel P; Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022 Nov 1;8(11):1571-1578. doi: 10.1001/jamaoncol.2022.3829.

Reference Type: DERIVED

PMID: 36048453 (View on PubMed)

Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.

Reference Type: DERIVED

PMID: 30575490 (View on PubMed)

Other Identifiers

NCIC CTG PA.6

Identifier Type: OTHER

Identifier Source: secondary_id

2011-002026-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Prodige 24 / Accord 24

Identifier Type: -

Identifier Source: org_study_id