FIrst Line Treatment of Metastatic Pancreatic Cancer: Sequential Nab-paclitaxel + Gemcitabine/FOLFIRI.3 VS Nab-paclitaxel + Gemcitabine (FIRGEMAX)

Phase II Randomised Multicenter Trial Evaluating a Sequential Treatment With Nab-paclitaxel+Gemcitabine /FOLFIRI.3 vs Nab-paclitaxel + Gemcitabine in First Line Metastatic Pancreatic Cancer

The main objective of this trial is to evaluate every 2 months alternating nab-paclitaxel/gemcitabine and FOLFIRI.3 versus nab-paclitaxel + gemcitabine, regarding the progression of disease at 6 months.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: FOLFIRI.3; Drug: nab-paclitaxel+ gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Albi, France
    • Clinique Privée Claude Bernard
  • Blois, France
    • CH
  • Bordeaux, France
    • Clinique Tivoli Ducos
  • Boulogne sur Mer, France
    • Hôpital Duchenne
  • Bourgoin-Jallieu, France
    • CH Pierre Oudot
  • Caen, France
    • Centre Francois Baclesse
  • Caen, France
    • CHR côte de Nacre
  • Corbeil Essonnes, France
    • Centre Hospitalier Sud Francilien
  • Dijon, France
    • Centre GF Leclerc
  • Draguignan, France
    • CH de la Dracénie
  • Flers, France
    • Ch Jacques Monod
  • Frejus, France
    • CH
  • Le Kremlin Bicetre, France
    • CHU
  • Le Mans, France
    • CH
  • Limoges, France
    • CHU
  • Limoges, France
    • Clinique Chenieux
  • Longjumeau -, France
    • CH
  • Lyon, France
    • CH Pierre Benite
  • Marseille, France, 13331
    • Hopital Europeen Marseille
  • Mont-de-Marsan, France
    • H Layné
  • Paris, France
    • Hôpital Cochin
  • Paris, France, 75651
    • Hopital La Pitie Salpetriere
  • Paris, France, 75020
    • HEGP
  • Perpignan, France
    • CH St Jean
  • Pessac, France
    • Hôpital Haut Levêque
  • Plérin, France
    • Centre Cario - Hpca Saint Brieuc
  • Romans Sur Isere, France
    • Hopitaux Drome Nord
  • Rouen, France
    • CHU
  • Saint Grégoire, France
    • CHP
  • Strasbourg, France
    • Clinique Privée
  • Thonon Les Bains, France
    • Hopitaux du Leman
  • Toulouse, France
    • Clinique Pasteur Groupe ONCORAD GARONNE
  • Toulouse, France
    • Clinique Privée Pasteur
  • Toulouse, France
    • Clinique Privée Saint Jean
  • Toulouse, France
    • Clinique St Jean Languedoc
  • Villejuif, France, 94805
    • Gustave Roussy
  • Villejuif, France
    • Hôpital Paul Brousse

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histological or cytological confirmation of pancreatic adenocarcinoma
• Distant metastatic disease
• Scan (or MRI if scanner contraindicated) completed within 3 weeks of the start of treatment
• At least one lesion measurable by RECIST v1.1 criteria
• Life expectancy> 3 months
• No previous chemotherapy (adjuvant chemotherapy with gemcitabine authorised if administered more than 6 months prior to inclusion)
• No previous radiotherapy (unless at least one measurable target lesion outside the irradiation zone)
• Pain must be monitored before inclusion
• 18 years < age < 75
• Performance status: WHO < 2
• ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3, haemoglobin ≥ 9 g/dL
• ASAT (SGOT), ALAT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases found
• Bilirubin ≤ 1.5 x ULN (patients drained by retrograde technique are includable), creatinine < 120 μmol/L, or MDRD creatinine clearance > 60 mL/min
• Women of childbearing age must have a negative pregnancy test (β HCG) before starting treatment
• Women of childbearing age as well as men (who have sexual intercourse with women of childbearing age) must agree to use effective contraception without interruption for the duration of treatment and 6 months after the administration of the last treatment dose
• Patient affiliated to the social security scheme
• Patient information and signature of informed consent

Exclusion Criteria:

• - Other types of pancreatic tumours, especially endocrine or acinar cell tumours
• Ampulloma
• Presence of meningeal or cerebral metastases, bone metastases
• Gilbert's syndrome
• Presence of neuropathy> grade 1 according to NCIC-CTC 4.0
• Contraindications specific to the studied treatments
• History of chronic diarrhoea or inflammatory disease of the colon or rectum, or of unresolved occlusion or sub-occlusion for which symptomatic treatment is being administered
• Other concomitant cancer or history of cancer during the 5 years, with the exception of a carcinoma in situ of the cervix or basal cell or squamous cell carcinoma, considered cured
• Significant history of heart or respiratory disease, including any history of interstitial pneumonia
• Patient already included in another clinical trial with an experimental molecule
• Women who are breast-feeding
• Persons deprived of liberty or under guardianship
• Unable to submit to medical monitoring during the trial due to geographical, social or psychological reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nab-paclitaxel + gemcitabine/FOLFIRI.3; Alternance of : 2 months with nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m², 30 min in IV, 3 injections follow by 1 week free); follow by 2 months with FOLFIRI.3 (irinotecan: 90 mg/m² at D1, acid folinic 400 mg/m², 5Fu continus: 2000 mg/m² IV 46 hours, and irinotecan at D3, 90 mg/m²) This alternance continus until progression	Drug: FOLFIRI.3; For each cycle : 1 week out of 2 - injection at Day1, J15 Irinotécan 90 mg/m² at day1 in perfusion over 60 min in Y of folinic acid Folinic Acid 400 mg/m² (or 200 mg/m² Elvorine) at Day 1 in perfusion over 2 hours 5FU continu 2000 mg/m² during 46 hours Irinotécan at 90 mg/m² in perfusion over 60 mn at Day 3 (when 5FU perfusion is over); Drug: nab-paclitaxel+ gemcitabine; For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over.
Active Comparator: nab-paclitaxel + gemcitabine; nab-paclitaxel (125 g/m² - 30 min in IV) + gemcitabine (1000 mg/m² - 30 min in IV) 3 injections follow by 1 week free, until progression	Drug: nab-paclitaxel+ gemcitabine; For each cycle : 3 weeks out of 4 - injection at Day 1, 8 and 15 Nab-paclitaxel : 125 mg/m² of nab-paclitaxel in perfusion over 30 mn. Gemcitabine 1000 mg/m² in perfusion over 30 mn immediately after Nab paclitaxel administration is over.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Alive and Without Radiological and/or Clinical Progression 6 Months After the Randomization	The primary endpoint was the rate of patients alive and progression-free 6 months after randomization. Progression was assessed by the investigator and defined radiologically according to RECIST v1.1 criteria and/or clinically as deterioration of general condition not related to treatment, palpable tumor masses on clinical examination (adenopathy, tumor hepatomegaly, peritoneal carcinosis), pleural effusion, ascites. Patients who progressed or died before 6 months were considered to have failed the primary endpoint at 6 months. The 6-month imaging was the imaging done at 6 months with a +/- 1 month window.	6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS):	Overall survival was defined as the time from the date of randomization to the patient's death (all causes). For alive patients, the date of last news was taken into account	Up to 2 years after the treatment start
Best Response	Best response is defined as the best response for each patient regarding imagerie taken during the treatment. Response was evalauted according to RECIST v1.1 over the entire treatment period according the investigator	Up to the end of treatment on the average of 12 months
Progression-free Survival (PFS)	It was defined as the time between t randomization and the date of the first radiological progression (RECIST 1.1 criteria) and/or clinical progression according to the investigator or death (whatever the cause is); Patients alive without progression were censored at date of last news	up to 12 months after randomization

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Collaborators: UNICANCER; GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Study Chair: Julien TAIEB, Pr, HEGP - Paris - France

Publications and helpful links

General Publications

• Rinaldi Y, Pointet AL, Khemissa Akouz F, Le Malicot K, Wahiba B, Louafi S, Gratet A, Miglianico L, Laharie H, Bouhier Leporrier K, Thirot Bidault A, Texereau P, Coriat R, Terrebonne E, Gouttebel MC, Malka D, Bachet JB, Lepage C, Taieb J; PRODIGE 37 Investigators/Collaborators. Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancerologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX). Eur J Cancer. 2020 Sep;136:25-34. doi: 10.1016/j.ejca.2020.05.018. Epub 2020 Jul 2.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: November 26, 2015
• First Submitted That Met QC Criteria: July 5, 2016
• First Posted (Estimated): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Gemcitabine
• Other Study ID Numbers: PRODIGE 37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED