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Etude : GEMFOX /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : GEMFOX

Nom :

Traitement : Métastasique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 28/02/2020
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Essai de phase 3 randomisé comparant le FOLFOX à la gemcitabine en 1ère ligne métastatique chez les patients avec un adénocarcinome du pancréas et non éligibles au FOLFIRINOX.

Spécialité : Organes digestifs
Localisation : C25 - Tumeur maligne du pancréas
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Pancreatic adenocarcinoma (PAC) incidence increases regularly in Western countries and it is expected to become the second leading cause of cancer-related mortality in 2020. The prognosis of this disease remains very poor with an overall 5-year survival rate less than 5%.
The FOLFIRINOX regimen (5-fluorouracil [5-FU], folinic acid, irinotecan, and oxaliplatin) and the combination of nab-paclitaxel with gemcitabine demonstrated to be more effective than gemcitabine alone, and are both validated as standard first-line treatment options for metastatic PAC. However, the use of FOLFIRINOX is limited to patients with ECOG performance status (PS) 0-1 and aged less than 75 years. Nab-paclitaxel is currently not reimbursed in France.

This trial is an open label, multicenter, randomized phase III trial comparing gemcitabine vs FOLFOX in patients with metastatic pancreatic adenocarcinoma and non-fit for FOLFIRINOX. Adults fulfilling inclusion criteria and non-inclusion criteria will be randomized between a FOLFOX arm and a gemcitabine arm. The primary endpoint is the overall survival (OS) at 24 months. The secondary objectives are : objective response rate and disease control rate (RECIST v1.1, in case of evaluable lesion), duration of response, duration of disease control, progression free survival (PFS), the evolution of biomarkers Ca 19-9 and CEA under treatment, the toxicities according to International Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, the safety of both arms, the quality of life, the dose intensity (DI) of each protocol, the Quality-Adjusted Survival, and the rate and type of second-line / third-line regimens chemotherapy. With an expected median survival time in the control group of 5 months, an accrual period of 3 years and a minimum follow-up period of 2 years, a total of 199 patients per group are required to detect a hazard ratio of 0.75 based on a 5% two-sided type I error rate and a power of 80%, leading to a total number of 400 patients to include.


Study arms:
- Active Comparator: Group I: Gemcitabine
Gemcitabine at 1000 mg/m²

- Active Comparator: Group II: Folfox
Oxaliplatin at 85 mg/m² ; Folinic acid 400 mg/m² (racemic form) or 200 mg/m² (L-form) and 5-FU 2400 mg/m²


Main objective f the trial:
To assess the efficacy of FOLFOX in comparison to gemcitabine in metastatic first-line in patients with pancreatic adenocarcinoma and non-fit for FOLFIRINOX.

Secondary objectives of the trial:
- The others efficacy parameters centered on the tumor: objective response rate and disease control rate (RECIST v1.1, in case of evaluable lesion), duration of response, duration of disease control
- The progression free survival (PFS)
- The evolution of biomarkers Ca 19-9 and CEA to assess their prognostic value at inclusion and their predictive value under treatment
- The toxicities according to International Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- The safety of both arms
- The quality of life
- The dose intensity (DI) of each protocol
- The Quality-Adjusted Survival
- The rate and type of second-line / third-line regimens chemotherapy

Phase : III

Stade : Métastasique

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,
4. Metastatic disease confirmed (stage IV),
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),
6. Age ≥18 years,
7. Patient non-fit for FOLFIRINOX, with ECOG performance status (PS) 0-2
8. For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required. An albumin infusion is not permitted before the inclusion test,
9. Haematological status: neutrophils (ANC) >1.5x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,
10. Adequate renal function: serum creatinine level <150μM,
11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
12. Total bilirubin ≤3 x ULN,
13. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
14. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
15. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment,
16. Affiliation to a French social security system (recipient or assign).

Critères de non-inclusion : 1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
2. Local or locally advanced disease (stage I to III),
3. Patient uses warfarin,
4. Patient receiving concomitant radiotherapy,
5. Uncontrolled hypercalcemia,
6. Pre-existing permanent neuropathy (NCI grade ≥2),
7. Poor nutritional status
8. Known dihydropyrimidine dehydrogenase (DPD) deficiency,
9. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
10. Treatment with any other investigational medicinal product within 28 days prior to study entry,
11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,
13. Known uncontrolled bacterial infection
14. History or active interstitial lung disease (ILD),
15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
16. Patients with known allergy to active substance or any excipient of study drugs,
17. Allergy to iodinated contrast product
18. Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine and concomitant administration of prophylactic phenytoin
19. Patients under legal protection or unable to consent
20. Participation in another interventional research
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04167007
Promoteur :
APHP
Type de sponsor : Institutionnel
APHP
75010 PARIS 10

Coordonnateur :
Professeur Jean-Baptiste BACHET
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier de Boulogne-sur-Mer - 33 rue Jacques Monod - 62200 BOULOGNE SUR MER

Investigateur :
Docteur Vincent BOURGEOIS

TEC / ARC / IDE :
Marion BRUMENT
m.brument@
ch-boulogne.fr
03.21.99.39.04

Ouverture de l'essai : OUVERT

MAJ : 16/01/2019