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

Pancreatic Adenocarcinoma (Ductal Adenocarcinoma) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526135
• Other study ID #: Prodige 24 / Accord 24
• Secondary ID: NCIC CTG PA.6201
• Status: Completed
• Phase: Phase 3
• Start date: April 16, 2012
• Est. completion date: July 16, 2021

Study information

• Verified date: January 2022
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 493
• Est. completion date: July 16, 2021
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma (Ductal Adenocarcinoma)

Intervention

Drug:
• 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)
• 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

Locations

Country	Name	City	State
Canada	The Royal Victoria Hospital - Cancer Care Program	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Dr Leon Richard Oncology Centre	Moncton	New Brunswick
Canada	The Moncton Hospital	Moncton
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University (Department of Oncology)	Montreal	Quebec
Canada	Ottawa Health Research Institute	Ottawa	Ontario
Canada	CHUQ - Hotel-Dieu de Quebec	Quebec
Canada	Allain Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre, University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program, Sault Area Hospital	Sault Ste. Marie
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Department of Medical Oncology Health Sciences North	Sudbury	Ontario
Canada	General Surgery - TGH Site, Univ. Health Network	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba, St. Boniface General Hospital	Winnipeg	Manitoba
France	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	Orleans
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	Hôpital de Brabois-CHU de Nancy	Vandœuvre-lès-Nancy
France	Centre Alexis Vautrin	Vandoeuvre Les Nancy

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Canadian Cancer Trials Group

Countries where clinical trial is conducted

Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival (DFS)	to compare disease-free survival (DFS) at 3 years between the experimental and control arms.	3 YEARS
Secondary	Overall survival		36 MONTHS
Secondary	Specific survival		36 MONTHS