Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Pancreatic Cancer

Randomized Phase II/III Trial Comparing Folririnox Association [Oxaliplatin / Irinotecan / LV5FU2] Versus Gemcitabine in First Line of Chemotherapy in Metastatics Pancreas Cancers Patients

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective as first-line therapy in treating pancreatic cancer.

PURPOSE: This randomized phase II/III trial is studying how well combination chemotherapy works as first-line therapy in treating patients with metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: oxaliplatin; Drug: gemcitabine hydrochloride

Detailed Description

OBJECTIVES:

Primary

• Compare the objective response rate in patients with metastatic adenocarcinoma of the pancreas treated with oxaliplatin, irinotecan, leucovorin calcium, and fluorouracil vs gemcitabine as first-line chemotherapy. (Phase II)
• Compare the survival of patients treated with these regimens. (Phase III)

Secondary

• Compare the toxicity of these regimens in these patients.
• Compare progression-free survival of patients treated with these regimens. (Phase III)
• Compare the overall response rate in patients treated with these regimens. (Phase III)
• Compare quality of life of patients treated with these regimens. (Phase III)

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oxaliplatin IV over 2 hours, irinotecan IV over 1½ hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days.
• Arm II: Patients receive gemcitabine IV on days 1, 8, 15, 22, 29, 36, and 43. Beginning on day 57, patients receive gemcitabine IV once weekly for 3 weeks (days 57, 64, and 71). Courses repeat every 28 days.

PROJECTED ACCRUAL: A total of 348 patients (88 for phase II and 260 for phase III) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • Centre Hospitalier Universitaire d'Amiens
  • Avignon, France, 84902
    • Hopital Duffaut
  • Belfort, France, 90000
    • Centre Hospitalier Général
  • Besancon, France, 25030
    • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
  • Bobigny, France, 93009
    • Hôpital Avicenne
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France, 33075
    • Hopital Saint André
  • Bordeaux, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Boulogne Sur Mer, France, 62200
    • Centre Hospitalier Docteur Duchenne
  • Boulogne-Billancourt, France, F-92104
    • Hôpital Ambroise Paré
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Caen, France, 14033
    • CHU de Caen
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Clermont-Ferrand, France, 63058
    • CHR Clermont Ferrand, Hotel Dieu
  • Colmar, France, 68024
    • Hôpitaux Civils de Colmar
  • Creteil, France, 94000
    • Centre Hospitalier Universitaire Henri Mondor
  • Dijon, France, 21034
    • Hôpital du Bocage
  • Dijon, France, 21079
    • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  • Elbeuf, France, 76503
    • Centre Hospitalier Intercommunal St. Aubin les Elbeuf
  • Epernay, France, 51200
    • Clinique Saint Vincent
  • La Roche Sur Yon, France, F-85025
    • Centre Hospitalier Departemental
  • Le Havre, France, 76600
    • CMC Les Ormeaux
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lille, France, F-59020
    • Hopital Saint Vincent de Paul
  • Lormont, France, 33310
    • Polyclinique des Quatre Pavillons
  • Lyon, France, 69437
    • Hopital Edouard Herriot - Lyon
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Lyon, France, 69317
    • Hôpital de la Croix Rousse
  • Marseille, France, 13385
    • CHU de la Timone
  • Marseille, France, 13915
    • CHU Nord
  • Marseille, France, 13291
    • Hôpital Ambroise Paré
  • Metz, France, 57038
    • Hopital Notre-Dame de Bon Secours
  • Mont-de-Marsan, France, 40000
    • Centre Hospitalier General de Mont de Marsan
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes-Saint Herblain, France, 44805
    • Centre Regional Rene Gauducheau
  • Orleans, France, 45067
    • CHR D'Orleans - Hopital de la Source
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75674
    • Hopital Saint Michel
  • Perpignan, France, 66046
    • Centre Hospitalier de Perpignan
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Reims, France, 51092
    • CHU - Robert Debre
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rennes, France, 35064
    • Centre Eugene Marquis
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint Brieuc, France, F-22015
    • Clinique Armoricaine de Radiologie
  • Saint Cloud, France, 92210
    • Centre Rene Huguenin
  • Sainte Foy Les Lyon, France, 69110
    • Clinique Charcot
  • Semur en Auxois, France, 21140
    • Centre Hospitalier de Semur en Auxois
  • Strasbourg, France, 67098
    • Hopital Universitaire Hautepierre
  • Strasbourg, France, 67065
    • Centre Paul Strauss
  • Tarbes, France, 65013
    • Centre hospitalier de Tarbes
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Tours, France, 37044
    • CHU de Tours
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • No other pancreatic tumor type, including either of the following:

    • Neuroendocrine tumor
    • Acinar cell tumor
  • Metastatic disease
• Measurable disease in an area not previously irradiated
• No cerebral metastases or meningeal involvement of the tumor

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (biliary drainage allowed)

Renal

• Creatinine < 120 mmol/L

Cardiovascular

• No prior myocardial infarction
• No prior angina
• No uncompensated cardiac or coronary insufficiency
• No symptomatic arrhythmia

Gastrointestinal

• No prior inflammatory bowel disease
• No prior chronic diarrhea
• No unresolved symptomatic occlusion or subocclusion of the bowel

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No ongoing active infection
• No other malignancy except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No contraindication to study treatment
• No other serious medical disorder that would preclude study treatment
• No psychiatric disorder or social or geographic situation that would preclude study participation
• Not detained or under the guardianship of another person

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No concurrent participation in another clinical trial using therapeutic experimental agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gemcitabine	Drug: gemcitabine hydrochloride
Experimental: Folfirinox	Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective response rate (Phase II)
Survival (Phase III)

Secondary Outcome Measures

Outcome Measure
Toxicity
Progression-free survival (Phase III)
Quality of life (Phase III)
Overall response rate (Phase III)

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Study Chair: Thierry Conroy, MD, Centre Alexis Vautrin

Publications and helpful links

General Publications

• Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
• Ychou M, Desseigne F, Guimbaud R, et al.: Randomized phase II trial comparing folfirinox (5FU/leucovorin [LV], irinotecan [I] and oxaliplatin [O]) vs gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): first results of the ACCORD 11 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-4516, 2007.
• Lambert A, Jarlier M, Gourgou Bourgade S, Conroy T. Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ ACCORD 11 randomized trial. PLoS One. 2017 Sep 20;12(9):e0183288. doi: 10.1371/journal.pone.0183288. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2004
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 30, 2010

Study Registration Dates

• First Submitted: June 2, 2005
• First Submitted That Met QC Criteria: June 2, 2005
• First Posted (Estimate): June 3, 2005

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Gemcitabine; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000430100; FRE-FNCLCC-ACCORD-11/0402; EU-20512

Drug and device information, study documents

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