Efficacy Of Gembrax Followed By Folfirinox Versus Folfirinox Alone In First Metastatic Line Pancreatic Cancer Patients

Study Overview

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

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.

Metastatic Pancreatic Cancer

COMBINATION_PRODUCT: GEMBRAX/FOLFIRINOX Arm A
COMBINATION_PRODUCT: FOLFIRINOX Arm B

PROICM 2021-02 GAB

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-09-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-08
First Submitted that Met QC Criteria 2021-10-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-22
First Posted (ACTUAL) 2021-10-04	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: GEMBRAX/FOLFIRINOX Arm A 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 400m	COMBINATION_PRODUCT: GEMBRAX/FOLFIRINOX Arm A 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
ACTIVE_COMPARATOR: FOLFIRINOX Arm B 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 maximu	COMBINATION_PRODUCT: FOLFIRINOX Arm B Patients in this arm received : A maximum of 3 cycles (6 months) of chemotherapy. One cycle = 4 administrations of FOLFIRINOX

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: GEMBRAX/FOLFIRINOX Arm A

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 400m

COMBINATION_PRODUCT: GEMBRAX/FOLFIRINOX Arm A

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

ACTIVE_COMPARATOR: FOLFIRINOX Arm B

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 maximu

COMBINATION_PRODUCT: FOLFIRINOX Arm B

Patients in this arm received : A maximum of 3 cycles (6 months) of chemotherapy. One cycle = 4 administrations of FOLFIRINOX

Primary Outcome Measures	Measure Description	Time Frame
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.	From randomization to disease progression or death, up to 6 month

Secondary Outcome Measures	Measure Description	Time Frame
Tolerance of treatments	Adverse events rate assessed according to the NCI-CTC AE classification in application	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.	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.	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.	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.	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").	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	At inclusion and when treatment is stopped (approximately 6 month)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Aurore MOUSSION, MD

Phone Number: 0467612446

Email: Aurore.Moussion@icm.unicancer.fr

Study Contact Backup

Name: Fabienne PORTALES, MD

Phone Number: 0467612353

Email: Fabienne.Portales@icm.unicancer.fr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

28 5. 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. 6. Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction within the past 6 months. 7. Peripheral sensory neuropathy ≥ grade 2 at the time of inclusion. 8. ECG with a QTc interval greater than 450 ms for men and greater than 470 ms for women 9. History of chronic inflammatory disease of the colon or rectum 10. 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) 11. Intolerance or allergy to one of the study drugs (gemcitabine, nab-paclitaxel, oxaliplatin, irinotecan, 5-FU) or to an excipient of one of the drugs (example: fructose) described in the sections Against SPC indications or Special Warnings and Precautions or Prescribing Information 12. Pregnant or breastfeeding women. Women of childbearing potential must have a negative pregnancy test (serum β-hCG) within 72 hours prior to inclusion. 13. Patients on anticoagulants (e.g., Coumadin) (modifications to treatment may be required prior to inclusion). 14. Treatment with brivudine within 4 weeks before or after treatment with 5-fluorouracil (due to a potentially fatal interaction). 15. Active and uncontrolled bacterial, viral, or fungal infections requiring systemic treatment. 16. Active HIV infection, known hepatitis B or C infection. 17. History of peripheral arterial disease (e.g., claudication, Buerger's disease), chronic inflammatory bowel disease or rectal disease, pulmonary fibrosis or interstitial pneumonia. 18. Administration of a live attenuated vaccine within 10 days before inclusion and up to 6 months post-treatment. 19. Patient refusal or inability to comply with study procedures. 20. Inability to undergo follow-up for geographical, social, or psychological reasons. 21. Participation in another clinical trial involving an investigational product within the 30 days prior to inclusion. 22. Legal incapacity (patient under guardianship or guardianship).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Fabienne PORTALES, MD, Institut de Cancérologie de Montpellier (ICM)

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Ferlay 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.
Burris 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.
Sultana 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.
Conroy 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.
Von 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.
Siegel 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.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record