Clinical trial NCT00112658: Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Pancreatic Cancer
Official title: Randomized Phase II/III Trial Comparing Folririnox Association [Oxaliplatin / Irinotecan / LV5FU2] Versus Gemcitabine in First Line of Chemotherapy in Metastatics Pancreas Cancers Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2005-06-03
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (Phase II)
measure: Survival (Phase III)
Secondary outcomes:
measure: Toxicity
measure: Progression-free survival (Phase III)
measure: Quality of life (Phase III)
measure: Overall response rate (Phase III)
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Avignon
country: France
facility: Hopital Duffaut
city: Belfort
country: France
facility: Centre Hospitalier General
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Clermont-Ferrand
country: France
facility: CHR Clermont Ferrand, Hotel Dieu
city: Colmar
country: France
facility: Hopitaux Civils de Colmar
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dijon
country: France
facility: Hopital Du Bocage
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Elbeuf
country: France
facility: Centre Hospitalier Intercommunal St. Aubin les Elbeuf
city: Epernay
country: France
facility: Clinique Saint Vincent
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Havre
country: France
facility: CMC Les Ormeaux
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Hopital Saint Vincent de Paul
city: Lormont
country: France
facility: Polyclinique des Quatre Pavillons
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Marseille
country: France
facility: Hopital Ambroise Pare
city: Marseille
country: France
facility: CHU de la Timone
city: Marseille
country: France
facility: CHU Nord
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier General de Mont de Marsan
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Saint Michel
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: CHU - Robert Debre
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Sainte Foy Les Lyon
country: France
facility: Clinique Charcot
city: Semur en Auxois
country: France
facility: Centre Hospitalier de Semur en Auxois
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Tarbes
country: France
facility: Centre Hospitalier de Tarbes
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: CHU de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Alexis Vautrin
name: Thierry Conroy, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.