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* D1, D8 and D15 GEMBRAX: Albumin bound paclitaxel 125mg / m² followed by Gemcitabine 1000mg / m² followed by 2 weeks of rest
* D29 and D43 FOLFIRINOX: Oxaliplatin 85mg / m², Irinotecan 180mg / m², Folinic acid 400 mg / m², 5-fluorouracil 400mg / m² in bolus followed by continuous administration over 46h at 2400mg / m² followed by 2 weeks of rest

D1, D15, D29 and D43 FOLFIRINOX: Oxaliplatin 85mg / m², Irinotecan 180mg / m², Folinic acid 400mg / m², 5-fluorouracil 400mg / m² as a bolus followed by continuous administration over 46h at 2.400mg / m² followed by 2 weeks of rest.

Patients in the experimental arm received sequential treatment: 3 cycles of GEMBRAX followed by 2 cycles of FOLFIRINOX

GABRINOX

Patients in this arm received reatment: 3 cycles of FOLFIRINOX

FOLFIRINOX

Aurore MOUSSION, MD

Fabienne PORTALES, MD

Gael ROTH, MD

François Ghiringhelli, MD

Damien BOTSEN, MD

Eric Assénat, MD

Jean-Pierre Bleuse, MD

Fabienne Portalès, MD

Fawzi KARA-SLIMANE, MD

Faiza KHEMISSA, MD

The aim of this study is to evaluate the efficacy of sequential treatment (Gabrinox) comprising Gembrax regimen (Gemcitabine -Abraxane) followed by the Folfirinox regimen (5FU, Oxaliplatin and Irinotecan) compared to folfirinox alone in patients treated in first metastatic line pancreatic cancer

Pancreatic cancer is the third leading cause of cancer death in 2016, surpassing breast cancer. It is estimated that by 2030 pancreatic cancer will become the second leading cause of cancer death after lung cancer.

Its prognosis is very poor, with a 5-year overall survival rate (OS) at all stages of 5.5%.

In France, its incidence doubled in men and tripled in women between 1982 and 2012. The World Standardized Rate (MSR) for men and women respectively was 4.9% and 2% in 1980 and 10.2% and 6.9% in 2012. This means an annual rate of change of 2.3 for men to 3.9 for women.

Its diagnosis is often late, carried out in 50% of cases at stage 4, with limited treatment options, explaining its low survival rate at 5 years.

Until 2011, gemcitabine remained the only validated standard with a median survival of 6 months.

Many combinations with gemcitabine have been evaluated but have shown no significant survival advantage over Gemzar alone.

The most promising results reported to date remain the combination of oxaliplatin, irinotecan and 5 fluoro-uracil (FOLFIRINOX), which became the standard metastatic first-line treatment thanks to the results of the phase III study, ACCORD11, randomizing gemcitabine to FFX with for the first time, a significant gain in median survival, progression-free survival and response rate in favor of the experimental arm of 6.8 months vs. 11.1 months respectively (\[HR 0.57, 95 % IC, 0.45-0.7 3\];p\<0.001), 3.3vs6.4 (\[HR 0.47, 95 % IC, 0.37- 0.59\];p\<0.001) et de 9.4 % vs 31.6 % ; p\>0.001.

In 2013, the combination gemcitabine nab-paclitaxel (GEMBRAX) showed, in a randomized phase III study, compared to gemcitabine, a significant gain in terms, median survival, survival without progression and response rate in favor of the experimental arm, respectively for gemcitabine vs GEMBRAX, 6.7 months vs 8.5 months (\[HR 0.72, 95 % IC, 0.62-0.83\];p\<0.001) ; 3.7vs 5.5. (\[HR 0.69, 95 % IC, 0.58- 0.82\];p\<0.001) et de 7 % vs 23% ; p\>0.001.

FOLFIRINOX and GEMBRAX, two chemotherapy protocols which have shown their effectiveness in the 1st metastatic line with a gain in terms of response rate, progression-free survival and median survival but with increased grade 3/4 toxicities, compared to treatment with gemcitabine.

For FOLFIRINOX: a neutropenia rate of 45.7% vs 21% including 5.4% of febrile neutropenia vs 1.2, a rate of diarrhea of 12.7% vs 1.8% and peripheral neuropathies of 9% vs 0

For GEMBRAX neutropenia 38% VS 27% including 3% febrile neutropenia VS 1%, 6% diarrhea vs 1% and peripheral neuropathy 17% vs 1%:

Given the high toxicities, only patients with favorable performance status are eligible to receive these regimens.

The sponsor therefore considered a new concept of sequential GABRINOX treatment combining GEMBRAX followed by FOLFIRINOX, which should make it possible, by reducing toxicities, to increase the response rate and at the same time progression-free survival and median survival.

The sponsor performed a phase 1/2 study evaluating this GABRINOX protocol with the main objective of determining the maximum tolerated dose and increasing the response rate. Phase 2 is encouraging with a disease control rate and an objective response rate of 84.2% and 64.9% respectively, progression-free survival at 10.5 months and overall survival at 15.1 months as well as a more favorable safety profile compared to non-sequential treatments (less neutropenia 34.5%, febrile neutropenia 3.5% and neurotoxicity 5.2%).

These encouraging results led the investigator to propose a phase 2 study comparing the standard first-line treatment regimen FOLFIRINOX with the sequential regimen GABRINOX with the main objective of comparing efficacy in terms of objective response rate.

Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients

Randomized Phase II Trial Evaluating the Efficacy of a Sequential Treatment Gemcitabine Plus Nab-paclitaxel (Gembrax) Followed by Folfirinox Versus Folfirinox Alone in Patients Treated in First Metastatic Line Pancreatic Cancer

All IPD that underlie results in a publication and all sutdy documents can be share.

To compare progression-free survival between the investigational gabrinox treatment and the standard FOLFIRINOX treatment in patients with metastatic 1st line pancreatic adenocarcinoma.

Progression-free survival defined as the time between randomization and the onset of the 1st documented progression or death from any cause.

Tumor progression is assessed according to the RECIST 1.1 criteria and by the centralized review.

Adverse events rate assessed according to the NCI-CTC AE classification in application

Objective response rate (best response during treatment) defined as the percentage of complete or partial response. The tumor response is evaluated according to the RECIST 1.1 criteria.

Disease control rate defined as the percentage of complete or partial response or stability.

The tumor response is evaluated according to the RECIST 1.1 criteria.

Overall survival defined as the time between randomization and the onset of death regardless of the cause.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life in patients with pancreatic cancer in clinical trials.

The module comprises 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). The QLQ-PAN26 uses for the question 31 to 56 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much").

Establish a biological database for the analysis of biological predictive factors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients	NCT05065801	Metastatic Panc...	GABRINOX FOLFIRINOX	18 Years - 75 Years	Institut du Cancer de Montpellier - Val d'Aurelle
Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients	NCT05065801	Metastatic Panc...	GABRINOX FOLFIRINOX	18 Years - 75 Years	Institut du Cancer de Montpellier - Val d'Aurelle
Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients	NCT05065801	Metastatic Panc...	GABRINOX FOLFIRINOX	18 Years - 75 Years	Institut du Cancer de Montpellier - Val d'Aurelle

Spots Global Cancer Trial Database for gabrinox

Every month we try and update this database with for gabrinox cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gabrinox

Every month we try and update this database with for gabrinox cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gabrinox cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.