Clinical trial NCT02352337: First-line Metastatic Pancreatic Cancer : FOLFIRINOX +/- LV5FU2 in Maintenance Versus Firgem
Official title: Randomised Phase II Study in Metastatic Pancreatic Cancer Evaluating FOLFIRINOX +/- LV5FU2 in Maintenance Versus Firgem in First-line
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: cancer
pancreatic cancer
metastatic pancreatic cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The pancreas cancer is the 4th cause of death. All stage confused, the survival at 5 years is note over 5 %. At metastatic stage, the pancreatic adenocarcinoma is an incurable disease with the survival median of 2-4 months without chemotherapy.

Up to 2011, gemcitabine was the only reference treatment of this type of cancer. But until, the FOLFIRINOX could permitted to improve significantly the overall survival (6,8 months with gemcitabine vs 11,1 months with FOLFIRINOX) and the progression free survival (3,3 months with gemcitabine vs 6,4 months with FOLFIRINOX) for patients under 76 years. Main toxicities of this treatment are hematological, gastrointestinal and neuropathy with apparition of sensitive neuropathy, reversible, related to oxaliplatin.

These results are on a population under 76 years old. In this study, the median age of patients at inclusion was 61 years old and FOLFIRINOX was still beneficial for patients more than 65 years old. Given the increase of proportion of patients than more of 65 years old with pancreatic cancer and given the increase of life expected, it is important to know the effectiveness and tolerance of such treatment for patient older than 65 years and 76 years.

FIRGEM is an original strategic sequential treatment witch alternates, every 2 month, 4 cycles of FOLFIRI.3 and 2 cycles of 3 injections of gemcitabine. There is no cross resistance known between this 2 treatments witch limit toxicities and preserve quality of life of patients. A Phase II trial testing this treatment regimen to classical regimen of gemecitabine, showed an overall survival of 11 months in the FIRGEM regimen and an overall survival of 8,2 months in the gemcitabine regimen. The rate of progression was 45% near of progression rate with FOLFIRINOX. Tolerance is close to that FOLFIRINOX regimen but this strategic doesn't induce limiting neurotoxicities and allow to use oxaliplatin in 2de line of treatment.

The trial propose to evaluate the effectiveness and tolerance of FOLFIRINOX regimen (8 cycles) with LV5FU2 in maintenance (that could increase the FOLFIRINOX tolerable without decrease efficiency), to FIRGEM regimen and to FOLFIRINOX (12 cycles) which is the reference regimen.


Eligibility criteria: Inclusion Criteria:

* Metastatic disease
* At least one mesurable lesion according to RECIST V1.1 criteria
* No prior chemotherapy (excepted if there is at least on lestion out of the irradition area)
* Age \> 18 years. A favorable adviced by an onco geriatrician would be mandatory for inclusion of patients older than 75 older
* Performance statut (WHO) 0-1
* Polynyclear ≥ 1500/mm3
* Bilirubine ≤ 1,5 fois la LSN, creatinin \< 120μmol / L
* Signed informed consent form

Exclusion Criteria:

* Another type of pancreas tumor, as endocrine tumor ou with acinous cells
* Ampulloma
* Cerebral or meningeal metastasis
* Gilbert disease
* Neuropathie \> or = grade 1
* Study treatments contraindication
* Uncontrolled diarrhoea or inflamatory disease of colon or rectum, or bowel obstruction or bowel sub-obstruction no resolved with specific treatment
* Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease prevent patient to receive study Cancer within the 5 years before inclusion, except for int situ cancer of the neck of the uterus or basal cell skin cancer
* Significant previous cardiac and respiratory disease
* Patient included in an other therapeutic study with experimental treatment
* Pregnancy or breast feeding
* Patient depreved of freedom or under gardianship
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Primary outcomes:
measure: Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization.
timeFrame: 6 months after randomization
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 3 years after the treatment start
measure: Progression-free Survival (PFS)
timeFrame: up to 12 months after randomization
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU - Hôtel Dieu
city: Auxerre
country: France
facility: CH
city: Avignon
country: France
facility: CH - Henri Duffaut
city: Bayonne
country: France
facility: Centre d'oncologie et de radiothérapie
city: Bayonne
country: France
facility: CH
city: Beauvais
country: France
facility: Ch - Ch Beauvais
city: Besançon
country: France
facility: CHU
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Boulogne-sur-Mer
country: France
facility: CH -Duchenne
city: Béziers
country: France
facility: Bezier Ch
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Colmar
country: France
facility: Hôpitaux Civils de Colmar
city: Compiègne
country: France
facility: CH Compiègne-Noyon
city: Corbeil-Essonnes
country: France
facility: CHG
city: Dijon
country: France
facility: CHU - Hôpital François Mitterand
city: Dunkerque
country: France
facility: CH
city: Grenoble
country: France
facility: CHU de Grenoble
city: Grenoble
country: France
facility: Institut Daniel Hollard / Groupe Hospitalier Mutualiste
city: Hyeres
country: France
facility: Clinique Sainte Marguerite
city: Jossigny
country: France
facility: CH Marne La Vallée Jossigny
city: La Roche Sur Yon
country: France
facility: CHD
city: Lille
country: France
facility: CHU - Claude Huriez
city: Lorient
country: France
facility: Hôpital du Scorff
city: Lyon
country: France
facility: CHU - Hôpital Edouard Herriot
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: La Timone
city: Marseille
country: France
facility: Hôpital Européen de Marseille
city: Marseille
country: France
facility: Hôpital privé
city: Meaux
country: France
facility: CH - Centre Hospitalier de Meaux
city: Nice
country: France
facility: Centre Antoine Lassagne
city: Orléans
country: France
facility: Hôpital de la Source -service HGE et cancérologie digestive
city: Orléans
country: France
facility: Hôpital de la Source- service d'oncologie
city: Paris
country: France
facility: CHU AP - HP - Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Groupe Hospitalier Saint Joseph
city: Paris
country: France
facility: Hôpital La Pitié Salpetière
city: Pau
country: France
facility: CH Pau
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: CHU - Charles Nicolle
city: Saint-Etienne
country: France
facility: CHU
city: Saint-Malo
country: France
facility: CH
city: Soissons
country: France
facility: CH
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Tarbes
country: France
facility: CH - Bigorra
city: Tours
country: France
facility: Hôpityal Trousseau
city: Valenciennes
country: France
facility: CH
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Villeneuve D'Ascq
country: France
facility: Hôpital Privé de Villeneuve d'Ascq
Study officials:
affiliation: MARSEILLE La Timone
name: DAHAN Laetitia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dahan L, Williet N, Le Malicot K, Phelip JM, Desrame J, Bouche O, Petorin C, Malka D, Rebischung C, Aparicio T, Lecaille C, Rinaldi Y, Turpin A, Bignon AL, Bachet JB, Seitz JF, Lepage C, Francois E; PRODIGE 35 Investigators/Collaborators. Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial. J Clin Oncol. 2021 Oct 10;39(29):3242-3250. doi: 10.1200/JCO.20.03329. Epub 2021 Jul 21.