Clinical trial NCT01526135: Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma
Official title: Multicentric Randomized Phase III Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus 5-fluorouracil, Leucovorin, Irinotecan and Oxaliplatin (mFolfirinox) in Patients With Resected Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Adenocarcinoma (Ductal Adenocarcinoma)
Keywords: National multicentric phase III superiority trial
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Trials Group
First posted: 2012-02-03
Enrollment: 493
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: disease-free survival (DFS)
timeFrame: 3 YEARS
Secondary outcomes:
measure: Overall survival
timeFrame: 36 MONTHS
measure: Specific survival
timeFrame: 36 MONTHS
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba, St. Boniface General Hospital
state: Manitoba
city: Moncton
country: Canada
facility: Dr Leon Richard Oncology Centre
state: New Brunswick
city: Barrie
country: Canada
facility: The Royal Victoria Hospital - Cancer Care Program
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Sudbury
country: Canada
facility: Department of Medical Oncology Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: General Surgery - TGH Site, Univ. Health Network
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University (Department of Oncology)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allain Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre, University of Saskatchewan
state: Saskatchewan
city: Moncton
country: Canada
facility: The Moncton Hospital
city: Quebec
country: Canada
facility: CHUQ - Hotel-Dieu de Quebec
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program, Sault Area Hospital
city: Amiens
country: France
facility: CHU Nord
city: Angers
country: France
facility: ICO Paul Papin
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clichy
country: France
facility: Hôpital Beaujon
city: Colmar
country: France
facility: Hôpital Louis Pasteur
city: Dijon
country: France
facility: CHU de Dijon - Site Bocage
city: La Roche Sur Yon
country: France
facility: CHD Vendée
city: Lille
country: France
facility: Hôpital Huriez
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: CHU Nord
city: Marseille
country: France
facility: CHU Timone Adulte
city: Marseille
country: France
facility: Fondation Ambroise Paré / Hôpital Européen
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Mont de Marsan
country: France
facility: CH Layné
city: Montpellier
country: France
facility: CHU De ST Eloi
city: Montpellier
country: France
facility: CRCL Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Orleans
country: France
facility: CHR Orléans - La Source
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint Joseph
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière
city: Perpignan
country: France
facility: Hôpital Saint-Jean
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Reims
country: France
facility: Centre hospitalier de Reims
city: Rouen
country: France
facility: CHU Rouen
city: Saint Herblain
country: France
facility: Centre René Gauducheau
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Tours
country: France
facility: Hôpital Trousseau
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpital de Brabois-CHU de Nancy
Study officials:
affiliation: Centre Alexis Vautrin-VANDOEUVRE LES NANCY
name: Thierry CONROY, PROF
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.