Back to resultsA Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma (NEOPAN)
Primary Purpose
Pancreatic Cancer, Carcinoma
Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Gemcitabine
Folinic Acid
5-Fluoro-uracil
Oxaliplatin
Irinotecan
L-folinic
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring locally advanced pancreatic carcinoma, FOLFIRINOX
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the pancreas
- Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
- Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or > 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)
- Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
- WHO Performance status (PS) 0-1
- Age ≥18 years
Patient with organ function as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
- Hemoglobin ≥ 10 g/dL
- Platelets (PTL) ≥ 75 x 10⁹/L
- Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Bilirubin ≤ 1.5 x ULN
- Creatinine ≤ 2 x ULN
- Albumin > 0.75 x lower limit of normal (LLN)
- Urea ≤ 2 x ULN
- Adequate vital functions
- Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.
- Patient information and signed informed consent form
- Public or private health insurance coverage
- Uracilemia < 16 ng/ml
Exclusion Criteria:
- Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
- Patient with metastasis or with history of metastasis
- Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
- Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
- Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
- Pregnant woman
- Fructose intolerance
- Patients currently treated by warfarin
- Persons deprived of liberty or under guardianship
- Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule
Sites / Locations
- Centre Hospitalier Intercommunal Aix-Pertuis
- CHU Amiens - Hôpital Nord
- CHU d'Angers
- Centre hospitalier d'Auxerre
- Centre hospitalier Henri Duffaut
- Hôpital Avicenne
- Institut Bergonié
- Polyclinique Bordeaux Nord
- CH Boulogne sur Mer
- CHU Côte de Nacre
- Centre François Baclesse
- Hôpital Trousseau
- Hôpitaux civils de Colmar
- CH de Dijon
- CHD Vendée
- Centre Hospitalier de Laon
- Centre Oscar Lambret
- CHU de Limoges
- Hôpital Edouard Herriot - Lyon
- Hôpital Saint Joseph Saint Luc
- Hôptal Européen
- Hôpital De La Timone
- Centre Hospitalier de Meaux
- Groupe Hospitalier du Havre Jacques Monod
- CHU Hotel Dieu
- Centre Antoine Lacassagne
- CHR d'Orléans La Source
- Hôpital Saint Antoine
- Groupe hospitalier Paris Saint Joseph
- Groupe hospitalier Pitié Salpétrière
- CH Annecy Genevois
- CHU - Robert Debre
- CHU Rouen
- Hôpital Privé des Côtes d'Armor
- Centre Regional René Gauducheau
- Centre Hospitalier de Saint Malo
- Institut de cancérologie Lucien Neuwirth
- CHI Elbeuf
- Clinique mutualiste de l'Estuaire
- Hôpital privé Saint Claude
- Centre Hospitalier de Soissons
- Centre Paul Strass
- Polyclinique de l'Ormeau-GROP
- Centre Hospitalier de Rangueil
- Gustave Roussy
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm A: Gemcitabine
Arm B: Folfirinox
Arm Description
Gemcitabine 1000 mg/m² IV infusion over 30 minutes on D1 of each week for the 4 weeks of the first cycle (1 cycle = 4 weeks). For the following five cycles, gemcitabine infusion on D1, D8, and D15 of each cycle, followed by 1 week without injection (i.e. in total 4 cycles over 24 weeks; with 19 administrations of Gemcitabine).
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion. 5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days. Treatment will be continued for 24 weeks (12 cycles).
Outcomes
Primary Outcome Measures
Progression-Free-Survival (PFS)
To compare Progression-Free-Survival (PFS) between the two treatment arms
Secondary Outcome Measures
Composite index for treatment early severe toxicity
Biliary tract infection Grade 3-4 + any grade 5 toxicities + chemotherapy interruption for toxicity during the first four cycles.
Adverse events (NCI-CTCAE version 4.0); observance of chemotherapy
Observance of chemotherapy
Overall Survival
The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether SRBT improves overall survival compared to standard of care.
Progression-free survival: pattern of failure
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Percentage of secondarily curative-intent surgery
Percentage of patients who will undergo an exeresis of their pancreatic tumor, with R0 resection confirmed by anatomopathic pathology.
Objective tumour response, disease control and their duration
Objective tumour response, disease control and their duration (RECIST version 1.1),
Time to treatment failure
Time to treatment failure
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02539537
Brief Title
A Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma
Acronym
NEOPAN
Official Title
A Randomized Phase III Trial Comparing Chemotherapy With Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 23, 2015 (Actual)
Primary Completion Date
February 2022 (Actual)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
French national multicentric phase III trial evaluating chemotherapy with Folfirinox or gemcitabine in locally advanced pancreatic carcinoma.
Detailed Description
Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Carcinoma
Keywords
locally advanced pancreatic carcinoma, FOLFIRINOX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
171 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Gemcitabine
Arm Type
Active Comparator
Arm Description
Gemcitabine 1000 mg/m² IV infusion over 30 minutes on D1 of each week for the 4 weeks of the first cycle (1 cycle = 4 weeks). For the following five cycles, gemcitabine infusion on D1, D8, and D15 of each cycle, followed by 1 week without injection (i.e. in total 4 cycles over 24 weeks; with 19 administrations of Gemcitabine).
Arm Title
Arm B: Folfirinox
Arm Type
Experimental
Arm Description
Administered once every 14 days for 24 weeks (12 cycles). A cycle equals 14 days with injection on D1 of each cycle. Treatment starts with oxaliplatin (85 mg/m²) administration; IV infusion over 2 hours, followed by the simultaneous administration (using a Y-tubing) of folinic acid 400 mg/m² (racemic) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours and irinotecan 180 mg/m² IV infusion over 90 minutes. The irinotecan will begin 30 minutes after the start of the folinic acid infusion.
5-Fluoro-uracil (5-FU) IV 2,400 mg/m²/h will be administered over 46 hours after the end of the folinic acid infusion, i.e. 1200 mg/m²/day for the duration of 2 days.
Treatment will be continued for 24 weeks (12 cycles).
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
Folinic Acid
Intervention Type
Drug
Intervention Name(s)
5-Fluoro-uracil
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Type
Drug
Intervention Name(s)
L-folinic
Primary Outcome Measure Information:
Title
Progression-Free-Survival (PFS)
Description
To compare Progression-Free-Survival (PFS) between the two treatment arms
Time Frame
From randomization until disease progression or date of death, assessed up until to 128 weeks
Secondary Outcome Measure Information:
Title
Composite index for treatment early severe toxicity
Description
Biliary tract infection Grade 3-4 + any grade 5 toxicities + chemotherapy interruption for toxicity during the first four cycles.
Time Frame
First four chemotherapy cycles, 16 weeks
Title
Adverse events (NCI-CTCAE version 4.0); observance of chemotherapy
Description
Observance of chemotherapy
Time Frame
During treatment phase, 24 weeks
Title
Overall Survival
Description
The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether SRBT improves overall survival compared to standard of care.
Time Frame
Until death, assessed up 128 weeks after randomization
Title
Progression-free survival: pattern of failure
Description
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Time Frame
Until Disease Progression, assessed uo until 128 weeks after randomization
Title
Percentage of secondarily curative-intent surgery
Description
Percentage of patients who will undergo an exeresis of their pancreatic tumor, with R0 resection confirmed by anatomopathic pathology.
Time Frame
Until surgery, if applicable, up until 128 weeks after randomization
Title
Objective tumour response, disease control and their duration
Description
Objective tumour response, disease control and their duration (RECIST version 1.1),
Time Frame
Until disease progression or date of death, assessed up until 128 weeks after randomization
Title
Time to treatment failure
Description
Time to treatment failure
Time Frame
From randomisation to the end of treatment
Title
Quality of life questionnaire - Core 30 (QLQ-C30)
Description
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.
Time Frame
assessed up until 128 weeks after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the pancreas
Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or > 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)
Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
WHO Performance status (PS) 0-1
Age ≥18 years
Patient with organ function as follows:
Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
Hemoglobin ≥ 10 g/dL
Platelets (PTL) ≥ 75 x 10⁹/L
Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
Bilirubin ≤ 1.5 x ULN
Creatinine ≤ 2 x ULN
Albumin > 0.75 x lower limit of normal (LLN)
Urea ≤ 2 x ULN
Adequate vital functions
Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.
Patient information and signed informed consent form
Public or private health insurance coverage
Uracilemia < 16 ng/ml
Exclusion Criteria:
Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
Patient with metastasis or with history of metastasis
Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
Pregnant woman
Fructose intolerance
Patients currently treated by warfarin
Persons deprived of liberty or under guardianship
Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel DUCREUX, Professor
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Intercommunal Aix-Pertuis
City
Aix-en-Provence
ZIP/Postal Code
13100
Country
France
Facility Name
CHU Amiens - Hôpital Nord
City
Amiens
Country
France
Facility Name
CHU d'Angers
City
Angers
Country
France
Facility Name
Centre hospitalier d'Auxerre
City
Auxerre
Country
France
Facility Name
Centre hospitalier Henri Duffaut
City
Avignon
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93000
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Polyclinique Bordeaux Nord
City
Bordeaux
ZIP/Postal Code
33077
Country
France
Facility Name
CH Boulogne sur Mer
City
Boulogne sur Mer
ZIP/Postal Code
62321
Country
France
Facility Name
CHU Côte de Nacre
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Centre François Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Hôpital Trousseau
City
Chambray-les-tours
Country
France
Facility Name
Hôpitaux civils de Colmar
City
Colmar
Country
France
Facility Name
CH de Dijon
City
Dijon
Country
France
Facility Name
CHD Vendée
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Centre Hospitalier de Laon
City
Laon
ZIP/Postal Code
02000
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
CHU de Limoges
City
Limoges
Country
France
Facility Name
Hôpital Edouard Herriot - Lyon
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Hôpital Saint Joseph Saint Luc
City
Lyon
Country
France
Facility Name
Hôptal Européen
City
Marseille
ZIP/Postal Code
13003
Country
France
Facility Name
Hôpital De La Timone
City
Marseille
ZIP/Postal Code
13365
Country
France
Facility Name
Centre Hospitalier de Meaux
City
Meaux
ZIP/Postal Code
77000
Country
France
Facility Name
Groupe Hospitalier du Havre Jacques Monod
City
Montivilliers
Country
France
Facility Name
CHU Hotel Dieu
City
Nantes
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
CHR d'Orléans La Source
City
Orléans
Country
France
Facility Name
Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Groupe hospitalier Paris Saint Joseph
City
Paris
Country
France
Facility Name
Groupe hospitalier Pitié Salpétrière
City
Paris
Country
France
Facility Name
CH Annecy Genevois
City
Pringy
Country
France
Facility Name
CHU - Robert Debre
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Rouen
City
Rouen
Country
France
Facility Name
Hôpital Privé des Côtes d'Armor
City
Saint Brieuc
ZIP/Postal Code
22190
Country
France
Facility Name
Centre Regional René Gauducheau
City
Saint Herblain
Country
France
Facility Name
Centre Hospitalier de Saint Malo
City
Saint Malo
ZIP/Postal Code
35403
Country
France
Facility Name
Institut de cancérologie Lucien Neuwirth
City
Saint Priest En Jarez
ZIP/Postal Code
42271
Country
France
Facility Name
CHI Elbeuf
City
Saint-Aubin-lès-Elbeuf
Country
France
Facility Name
Clinique mutualiste de l'Estuaire
City
Saint-Nazaire
Country
France
Facility Name
Hôpital privé Saint Claude
City
Saint-quentin
Country
France
Facility Name
Centre Hospitalier de Soissons
City
Soissons
ZIP/Postal Code
02209
Country
France
Facility Name
Centre Paul Strass
City
Strasbourg
Country
France
Facility Name
Polyclinique de l'Ormeau-GROP
City
Tarbes
Country
France
Facility Name
Centre Hospitalier de Rangueil
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Gustave Roussy
City
Villejuif
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
IPD Sharing Time Frame
The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
IPD Sharing Access Criteria
Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
Learn more about this trial
A Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma
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