Metastatic Pancreatic CancerPhase 2GABRINOX2NCT05065801
Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients
A Phase 2 study testing GEMBRAX/FOLFIRINOX Arm A and FOLFIRINOX Arm B in people with Metastatic Pancreatic Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 8 sites in France.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- GEMBRAX/FOLFIRINOX Arm A and FOLFIRINOX Arm B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 8 sitesFrance
- Study dates
- 11 Jan 2022to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 18 to 75 on the date the consent is signed.
- Histologically or cytologically proven metastatic pancreatic adenocarcinoma. The definitive diagnosis of pancreatic adenocarcinoma metastases will be made by integrating the histopathological data in the context of the radiological data.
- One or more metastatic lesion (s) measurable (Recist 1.1) by Thoraco-Abdomino-Pelvic scanner (or hepatic MRI and Thoraco-Abdomino-Pelvic scanner not injected, if the patient is allergic to the product of contrast).
- Previous treatment (including radiochemotherapy) for the non-metastatic disease authorized if a delay ≥ 6 months between the last treatment and the recurrence is respected.
- WHO performance status ≤ 1
- Uracilemia <16 ng / ml
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- Acceptable hematological assessment at inclusion (obtained within 14 days before the start of treatment) defined by: • Neutrophils ≥ 2 × 109 / L; • Platelets ≥ 100,000 / mm3 (100 × 109 / L); • Hemoglobin ≥ 9 g / dl.
- Acceptable renal and hepatic function at inclusion (obtained within 14 days before the start of treatment) defined by: • AST and ALT ≤ 2.5 x upper limit of the norm (ULN), unless liver metastases are present in this case AST and ALT ≤ 5 × ULN is allowed; • Total bilirubin ≤ 1.5 x ULN; • Serum creatinine within the norm limits or calculated clearance ≥ 50ml / min for patients with a serum creatinine value above or below the norm values (clearance calculated by the CKD-EPI formula).
- Calcemia AND magnesemia AND kalaemia ≥ LLN and ≤ 1.2 x ULN
- If the patient is sexually active, he must agree to use contraception deemed adequate and appropriate by the investigator throughout the period of administration of the study drug and up to 6 months after discontinuation of treatment for women and for men.
- Signature of consent before any procedure specific to the study.
- Affiliated with the French national social security.
Who cannot join
- Known brain metastasis.
- Previous treatment with radiotherapy, surgery, chemotherapy or experimental therapy for the treatment of metastatic disease.
- Major surgery, other than diagnostic surgery (that is, surgery done to obtain a diagnostic biopsy without organ harvesting), within 4 weeks of day 1 of study treatment.
- Known Gilbert's syndrome or homozygous for know UGT1A1 * 28
- Other concomitant cancer or history of cancer, except cervical cancer in situ treated, skin basal or squamous cell carcinoma, superficial bladder tumor (Ta, Tis, and T1) or a tumor with a good prognosis treated curatively without chemotherapy and without any sign of disease in the 3 years preceding inclusion.
- Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction within the past 6 months.
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- Peripheral sensory neuropathy ≥ grade 2 at the time of inclusion.
- ECG with a QTc interval greater than 450 ms for men and greater than 470 ms for women
- Any other concomitant and unbalanced disease or serious disturbance that may interfere with the patient's participation in the study and his safety during the study (eg severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders)
- Allergy or intolerance to any study drug (gemcitabine, nab-paclitaxel, oxaliplatin, irinotecan, 5-FU) or any excipient (e.g., fructose) as described in the sections " contraindication or special warnings and precautions" or "prescribing information" of the summary of product characteristics indications.
- Pregnant or breastfeeding women. Women of childbearing potential must have a negative pregnancy test (serum β-hCG) within 72 hours prior to inclusion.
- Patients on vitamin K antagonists (e.g., Coumadin) (modifications to treatment may be required prior to inclusion).
- Treatment with brivudine within 4 weeks before or after treatment with 5-fluorouracil (due to a potentially fatal interaction).
- Active and uncontrolled bacterial, viral, or fungal infections requiring systemic treatment.
- Active HIV infection, known hepatitis B or C infection.
- History of peripheral arterial disease (e.g., claudication, Buerger's disease), chronic inflammatory bowel disease or rectal disease, pulmonary fibrosis or interstitial pneumonia.
- Administration of a live attenuated vaccine within 10 days before inclusion and up to 6 months post-treatment.
- Patient refusal or inability to comply with study procedures.
- Inability to undergo follow-up for geographical, social, or psychological reasons.
- Participation in another clinical trial involving an investigational product within the 30 days prior to inclusion.
- Legal incapacity (patient under guardianship or guardianship).
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
France8 sites, 7 recruiting
- Recruiting
Centre Georges-François Leclerc
Dijon, 21079
François Ghiringhelli, MD, FGhiringhelli@cgfl.fr
- Not yet recruiting
CHU Grenoble
Grenoble, Auvergne-Rhône-Alpes, 38000
Gael ROTH, MD, GRoth@chu-grenoble.fr
- Recruiting
CHU St Eloi
Montpellier, Herault, 34295
Eric Assénat, MD, 04 67 33 67 33, e-assenat@chu-montpellier.fr
- Recruiting
Institut régional du Cancer de Montpellier
Montpellier, Hérault, 34298
Aurore MOUSSION
Fabienne Portalès, MD
- Not yet recruiting
Centre Catalan d'Oncologie
Perpignan, Pyrénées-Orientales, 66000
Fawzi KARA-SLIMANE, MD, fawzi.karaslimane@cco-perpignan.fr
- Recruiting
CH de Perpignan
Perpignan, Pyrénées-Orientales, 66046
Faiza KHEMISSA, MD, faiza.khemissa@ch-perpignan.fr
- Recruiting
Institut GODINOT
Reims, Grand Est, 51100
Damien BOTSEN, MD, damien.botsen@reims.unicancer.fr
- Active, not recruiting
CHU St Etienne
Saint-Etienne, Auvergne-Rhône-Alpes, 42000
About this study
Official title: 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
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
Read the detailed description
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.
- Conditions
- Metastatic Pancreatic Cancer
- Being tested
- GEMBRAX/FOLFIRINOX Arm A, FOLFIRINOX Arm B
- Keywords
- pancreatic, cancer
- Medical subject headings
- Pancreatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEMBRAX/FOLFIRINOX Arm ACombination product
Patients in the experimental arm received sequential treatment: A maximum of 6 cycles (12 months) of chemotherapy; One cycle = 3 administrations of GEMBRAX followed by 2 administrations of FOLFIRINOX
FOLFIRINOX Arm BCombination product
Patients in this arm received : A maximum of 3 cycles (6 months) of chemotherapy. One cycle = 4 administrations of FOLFIRINOX
| Study group | Role | What they receive |
|---|---|---|
| GEMBRAX/FOLFIRINOX Arm A | Experimental | One cycle:
* 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.
A maximum of 6 cycles (12 months) of chemotherapy will be administered to patients in arm A. Receives: Combination Product: GEMBRAX/FOLFIRINOX Arm A |
| FOLFIRINOX Arm B | Active comparator | One cycle :
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.
A maximum of 3 cycles (6 months) of chemotherapy will be administered to patients in arm B. Receives: Combination Product: FOLFIRINOX Arm B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
To compare progression-free survival between the investigational treatment (Arm A) and the standard treatment (Arm B) 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.
Measured: From randomization to disease progression or death, up to 6 month
Secondary outcomes (7)
Tolerability of treatments
Adverse events rate assessed according to the NCI-CTC AE V5.0 classification in application
Measured: From randomization to 30 days after end of treatment, up to 13 month for Arm A and 7 month for Arm B
Objective response rate
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.
Measured: From randomization to the best response (complete or partial response) during treatment, up to 6 month
Disease control rate
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.
Measured: From randomization to the complete or partial response or stability, up to 6 month
Overall survival
Overall survival defined as the time between randomization and the onset of death regardless of the cause.
Measured: From randomization to death, up to 2 years
Quality of life questionnaire -Core 30 (QLQ-C30)
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.
Measured: At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)
Quality of life questionnaire -PAN 26
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").
Measured: At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)
Collection of circulating tumor DNA (ctDNA)
Establish a biological database for the analysis of biological predictive factors
Measured: At inclusion and when treatment is stopped (approximately 6 month)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start11 Jan 2022
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fabienne PORTALES, MD, Study chair, Institut de Cancérologie de Montpellier (ICM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05065801
- Sponsor's protocol ID
- PROICM 2021-02 GAB
- Acronym
- GABRINOX2
- Status last verified
- Apr 2026
- First submitted
- 20 Sep 2021
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be available after publication of the results in peer-reviewed revues, and in national and international meetings. It includes all de-identified participants' data, the study protocol, the statistical analysis plan and the clinical study report. The corresponding author will provide data and datasets generated and/or analyzed during the study upon reasonable request.
Publications
Portales F, Gourgou S, Fiess C, Salasc F, Assenat E, Ychou M. GABRINOX-2 protocol: a French, prospective, multicentre, randomised phase II trial evaluating gemcitabine/nab-paclitaxel followed by FOLFIRINOX versus FOLFIRINOX alone as first-line treatment for metastatic pancreatic cancer. BMJ Open. 2025 Aug 16;15(8):e104228. doi: 10.1136/bmjopen-2025-104228.
PubMed 40819868Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncol. 2016 Sep-Oct;55(9-10):1158-1160. doi: 10.1080/0284186X.2016.1197419. Epub 2016 Aug 23.
PubMed 27551890Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
PubMed 9196156Sultana A, Smith CT, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2007 Jun 20;25(18):2607-15. doi: 10.1200/JCO.2006.09.2551.
PubMed 17577041Conroy 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.
PubMed 21561347Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
PubMed 24131140Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
PubMed 28055103
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05065801
- Acronym / sponsor ID
- GABRINOX2 / PROICM 2021-02 GAB
- Conditions
- Metastatic Pancreatic Cancer
- Keywords
- pancreatic, cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Study start
- 11 Jan 2022 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 4 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GEMBRAX/FOLFIRINOX Arm A | Experimental | Combination Product: GEMBRAX/FOLFIRINOX Arm AOne cycle: * 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. A maximum of 6 cycles (12 months) of chemotherapy will be administered to patients in arm A. |
| FOLFIRINOX Arm B | Active comparator | Combination Product: FOLFIRINOX Arm BOne cycle : 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. A maximum of 3 cycles (6 months) of chemotherapy will be administered to patients in arm B. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female aged 18 to 75 on the date the consent is signed.
- Histologically or cytologically proven metastatic pancreatic adenocarcinoma. The definitive diagnosis of pancreatic adenocarcinoma metastases will be made by integrating the histopathological data in the context of the radiological data.
- One or more metastatic lesion (s) measurable (Recist 1.1) by Thoraco-Abdomino-Pelvic scanner (or hepatic MRI and Thoraco-Abdomino-Pelvic scanner not injected, if the patient is allergic to the product of contrast).
- Previous treatment (including radiochemotherapy) for the non-metastatic disease authorized if a delay ≥ 6 months between the last treatment and the recurrence is respected.
- WHO performance status ≤ 1
Key exclusion criteria (21 listed)
- Known brain metastasis.
- Previous treatment with radiotherapy, surgery, chemotherapy or experimental therapy for the treatment of metastatic disease.
- Major surgery, other than diagnostic surgery (that is, surgery done to obtain a diagnostic biopsy without organ harvesting), within 4 weeks of day 1 of study treatment.
- Known Gilbert's syndrome or homozygous for know UGT1A1 * 28
- Other concomitant cancer or history of cancer, except cervical cancer in situ treated, skin basal or squamous cell carcinoma, superficial bladder tumor (Ta, Tis, and T1) or a tumor with a good prognosis treated curatively without chemotherapy and without any sign of disease in the 3 years preceding inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GEMBRAX/FOLFIRINOX Arm APatients in the experimental arm received sequential treatment: A maximum of 6 cycles (12 months) of chemotherapy; One cycle = 3 administrations of GEMBRAX followed by 2 administrations of FOLFIRINOX | Combination product | GEMBRAX/FOLFIRINOX Arm A |
| FOLFIRINOX Arm BPatients in this arm received : A maximum of 3 cycles (6 months) of chemotherapy. One cycle = 4 administrations of FOLFIRINOX | Combination product | FOLFIRINOX Arm B |
Primary outcome
Progression-free survival
Time frame: From randomization to disease progression or death, up to 6 month
To compare progression-free survival between the investigational treatment (Arm A) and the standard treatment (Arm B) 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.
7 secondary outcomes
Tolerability of treatments
Time frame: From randomization to 30 days after end of treatment, up to 13 month for Arm A and 7 month for Arm B
Objective response rate
Time frame: From randomization to the best response (complete or partial response) during treatment, up to 6 month
Disease control rate
Time frame: From randomization to the complete or partial response or stability, up to 6 month
Overall survival
Time frame: From randomization to death, up to 2 years
Quality of life questionnaire -Core 30 (QLQ-C30)
Time frame: At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)
Quality of life questionnaire -PAN 26
Time frame: At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)
Collection of circulating tumor DNA (ctDNA)
Time frame: At inclusion and when treatment is stopped (approximately 6 month)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Background: PubMed 40819868Portales F, Gourgou S, Fiess C, Salasc F, Assenat E, Ychou M. GABRINOX-2 protocol: a French, prospective, multicentre, randomised phase II trial evaluating gemcitabine/nab-paclitaxel followed by FOLFIRINOX versus FOLFIRINOX alone as first-line treatment for metastatic pancreatic cancer. BMJ Open. 2025 Aug 16;15(8):e104228. doi: 10.1136/bmjopen-2025-104228.
- Background: PubMed 27551890Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. Acta Oncol. 2016 Sep-Oct;55(9-10):1158-1160. doi: 10.1080/0284186X.2016.1197419. Epub 2016 Aug 23.
- Background: PubMed 9196156Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
- Background: PubMed 17577041Sultana A, Smith CT, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2007 Jun 20;25(18):2607-15. doi: 10.1200/JCO.2006.09.2551.
- Background: PubMed 21561347Conroy 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.
- Background: PubMed 24131140Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
- Background: PubMed 28055103Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
- Descriptive epidemiology of cancers in metropolitan France: incidence, survival and prevalence. Cowppli-Bony A, Colonna M, Ligier K, Jooste V, Defossez G, Monnereau A, et al.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. All data will be available after publication of the results in peer-reviewed revues, and in national and international meetings. It includes all de-identified participants' data, the study protocol, the statistical analysis plan and the clinical study report. The corresponding author will provide data and datasets generated and/or analyzed during the study upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fabienne PORTALES, MD study chair
Institut de Cancérologie de Montpellier (ICM)
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GEMBRAX/FOLFIRINOX Arm A and FOLFIRINOX Arm B in people with Metastatic Pancreatic Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aurore MOUSSION, MD (0467612446 ext. +33, Aurore.Moussion@icm.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: From randomization to disease progression or death, up to 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05065801, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.