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Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients (GABRINOX2)

Primary Purpose

Metastatic Pancreatic Cancer

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

GABRINOX

FOLFIRINOX

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring pancreatic, cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 6. Uracilemia <16 ng / ml

7. 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.

8. 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 MCDK-EPI formula).

9. Calcemia AND magnesemia AND kalaemia ≥ LIN and ≤ 1.2 x ULN 10. 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 9 months after discontinuation of treatment. for women and 6 months for men.

11. Signature of consent before any procedure specific to the study. 12. Affiliated with the French national social security.

Exclusion Criteria:

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 validated 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.
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
Arterial or venous thrombotic or embolic events such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months of the start of treatment.
History of chronic inflammatory disease of the colon or rectum
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)
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
Legal incapacity (patient under guardianship or guardianship)

Sites / Locations

Centre Georges-François Leclerc
Institut GODINOTRecruiting
CHU St Eloi
Institut régional du Cancer de MontpellierRecruiting
Centre Catalan d'Oncologie
CH de Perpignan

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GABRINOX

FOLFIRINOX

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression-free survival

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.

Secondary Outcome Measures

Tolerance of treatments

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

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.

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.

Overall survival

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

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.

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").

Collection of circulating tumor DNA (ctDNA)

Establish a biological database for the analysis of biological predictive factors

Full Information

NCT ID

NCT05065801

First Posted

September 20, 2021

Last Updated

September 25, 2023

Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

1. Study Identification

Unique Protocol Identification Number

NCT05065801

Brief Title

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

Acronym

GABRINOX2

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 30, 2022 (Actual)

Primary Completion Date

March 30, 2027 (Anticipated)

Study Completion Date

November 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Pancreatic Cancer

Keywords

pancreatic, cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

162 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GABRINOX

Arm Type

Experimental

Arm Description

Arm Title

FOLFIRINOX

Arm Type

Active Comparator

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

GABRINOX

Intervention Description

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

Intervention Type

Combination Product

Intervention Name(s)

FOLFIRINOX

Intervention Description

Patients in this arm received reatment: 3 cycles of FOLFIRINOX

Primary Outcome Measure Information:

Title

Progression-free survival

Description

Time Frame

From randomization to disease progression or death, up to 6 month

Secondary Outcome Measure Information:

Title

Tolerance of treatments

Description

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

Time Frame

From randomization to 30 days after end of treatment, up to 19 month

Title

Objective response rate

Description

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.

Time Frame

From randomization to the best response (complete or partial response) during treatment, up to 6 month

Title

Disease control rate

Description

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.

Time Frame

From randomization to the complete or partial response or stability, up to 6 month

Title

Overall survival

Description

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

Time Frame

From randomization to death, up to 2 years

Title

Quality of life questionnaire -Core 30 (QLQ-C30)

Description

Time Frame

At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)

Title

Quality of life questionnaire -PAN 26

Description

Time Frame

At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years)

Title

Collection of circulating tumor DNA (ctDNA)

Description

Establish a biological database for the analysis of biological predictive factors

Time Frame

At inclusion and when treatment is stopped (approximately 6 month)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 6. Uracilemia <16 ng / ml 7. 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. 8. 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 MCDK-EPI formula). 9. Calcemia AND magnesemia AND kalaemia ≥ LIN and ≤ 1.2 x ULN 10. 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 9 months after discontinuation of treatment. for women and 6 months for men. 11. Signature of consent before any procedure specific to the study. 12. Affiliated with the French national social security. Exclusion Criteria: 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. 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 History of chronic inflammatory disease of the colon or rectum 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) 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 Legal incapacity (patient under guardianship or guardianship)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aurore MOUSSION, MD

Phone

0467612446

Ext

+33

Aurore.Moussion@icm.unicancer.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Fabienne PORTALES, MD

Phone

0467612353

Ext

+33

Fabienne.Portales@icm.unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fabienne PORTALES, MD

Organizational Affiliation

Institut de Cancérologie de Montpellier (ICM)

Official's Role

Study Chair

Facility Information:

Facility Name

Centre Georges-François Leclerc

City

Dijon

State/Province

Côte d'Or

ZIP/Postal Code

21079

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

François Ghiringhelli, MD

FGhiringhelli@cgfl.fr

Facility Name

Institut GODINOT

City

Reims

State/Province

Grand Est

ZIP/Postal Code

51100

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Damien BOTSEN, MD

damien.botsen@reims.unicancer.fr

Facility Name

CHU St Eloi

City

Montpellier

State/Province

Herault

ZIP/Postal Code

34295

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eric Assénat, MD

Phone

04 67 33 67 33

e-assenat@chu-montpellier.fr

Facility Name

Institut régional du Cancer de Montpellier

City

Montpellier

State/Province

Hérault

ZIP/Postal Code

34298

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean-Pierre Bleuse, MD

First Name & Middle Initial & Last Name & Degree

Fabienne Portalès, MD

Facility Name

Centre Catalan d'Oncologie

City

Perpignan

State/Province

Pyrénées-Orientales

ZIP/Postal Code

66000

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fawzi KARA-SLIMANE, MD

fawzi.karaslimane@cco-perpignan.fr

Facility Name

CH de Perpignan

City

Perpignan

State/Province

Pyrénées-Orientales

ZIP/Postal Code

66046

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Faiza KHEMISSA, MD

faiza.khemissa@ch-perpignan.fr

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

IPD Sharing Time Frame

6 years

IPD Sharing Access Criteria

The data of the participants will be available on request and with a contract between the promoter and the applicant. The study protocol, the statistical analysis plan and the analytical code may also be the subject of data sharing under a transfer contract (GDPR-EU).

Citations:

PubMed Identifier

27551890

Citation

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.

Results Reference

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PubMed Identifier

9196156

Citation

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.

Results Reference

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PubMed Identifier

17577041

Citation

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.

Results Reference

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PubMed Identifier

21561347

Citation

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.

Results Reference

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PubMed Identifier

24131140

Citation

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.

Results Reference

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Links:

URL

https://linkinghub.elsevier.com/retrieve/pii/S0007455119300670

Description

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.

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

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