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Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer (Néofirinox)

Primary Purpose

Cancer of the Rectum

Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
mFolfirinox
Radiotherapy 50 Gy
Capecitabine
TME surgery
mFolfox6 or capecitabine
Sponsored by
UNICANCER
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer of the Rectum focused on measuring rectum, cancer, locally advanced

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically proven rectal adenocarcinoma
  • Stages cT3 with risk of local recurrence or cT4, M0 and for which a multidisciplinary meeting recommend preoperative CRT
  • Resectable tumor, or considered as potentially resectable after CRT
  • No distant metastases
  • Patient eligible for surgery
  • Patient aged from 18 to 75 years
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0/2.
  • No heart failure or coronary heart disease symptoms (even controlled).
  • No peripheral neuropathy > grade 1
  • No prior radiotherapy of the pelvis for any reason and no previous CT
  • No major comorbidity that may preclude the delivery of treatment and no active infection (HIV or chronic hepatitis B or C).
  • Adequate contraception in fertile patients.
  • Adequate hematologic function
  • Adequate hepatic function
  • Signed written informed consent

Exclusion Criteria:

  • Metastatic disease
  • Unresectable rectal cancer, including prostatic involvement or extension to pelvic floor muscles
  • Contraindication to 5-FU, or to oxaliplatin or to irinotecan, including Gilbert disease or genotype UGT1A1
  • Medical history of chronic diarrhea or inflammatory disease of the colon or rectum
  • Medical history of angina pectoris or myocardial infarction
  • Progressive active infection or any other severe medical condition that could jeopardize treatment administration
  • Other concomitant cancer, or medical history of cancer other than treated in situ cervical carcinoma or basocellular carcinoma or spinocellular carcinoma
  • Patient included in another clinical trial testing an investigational agent.
  • Pregnant or breast-feeding woman.
  • Persons deprived of liberty or under guardianship or incapable of giving consent
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.

Sites / Locations

  • Centre hospitalier Universitaire d'Amiens
  • ICO - Site Paul Papin
  • Centre hospitalier d'Auxerre
  • Centre Hospitalier de Beauvais
  • Institut de Cancérologie de Franche Comté
  • Centre Hospitalier de Blois
  • Hopital Avicenne
  • Clinique Tivoli
  • Hopital Saint Andre
  • Institut Bergonie
  • Centre Francois Baclesse
  • Chd de La Roche Sur Yon - Les Oudairies
  • Centre Bourgogne
  • Centre Oscar Lambret
  • Centre Léon Bérard
  • Hopital Prive Jean Mermoz
  • Ap Hm - Hopital de La Timone - Adultes
  • Institut de Cancérologie de Franche Comté
  • Centre Azuréen de cancérologie
  • Hopital Emile Muller
  • centre Alexis Vautrin
  • Polyclinique de Gentilly
  • Centre Antoine Lacassagne
  • Groupe Hospitalier La Pitie-Salpetriere
  • Institut Mutualiste Montsouris
  • Hopital Haut Leveque
  • Centre Hospitalier Regional D'Annecy
  • Hopital Robert Debre
  • Institut Jean Godinot
  • Clinique Armoricaine de Radiologie
  • Hopital Saint Gregoire
  • Clinique Mutualiste de L'Estuaire
  • Centre Hospitalier de la Réunion - Site du GHSR
  • ICO - Site René Gauducheau
  • Centre Paul Strauss
  • Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A : Radiotherapy + capecitabine

Arm B : Chemotherapy then radiochemotherapy

Arm Description

Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.

Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): oxaliplatin: 85 mg/m² in 2 hours at D1 irinotecan: 180 mg/m² in 90 min at D1 folinic acid: 400 mg/m² simultaneously in 2 hours at D1 during the irinotecan infusion 5-fluorouracil (5-FU): 2400 mg/m² continuous infusion during 48 hours (1200 mg/m² at D1 and D2), every 14 days during 2 months (4 cycles). Then followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.

Outcomes

Primary Outcome Measures

disease-free survival
To compare the 3-year disease-free survival between the investigational arm and the control arm.

Secondary Outcome Measures

Overall survival
Overall survival will be defined as the time from randomisation to the time of occurrence of the first death regardless to its cause. Patients alive at the time of analysis will be censored at the date of the last follow up.

Full Information

First Posted
March 1, 2013
Last Updated
August 30, 2023
Sponsor
UNICANCER
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1. Study Identification

Unique Protocol Identification Number
NCT01804790
Brief Title
Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer
Acronym
Néofirinox
Official Title
Randomized Phase III Study Comparing Preoperative Chemoradiotherapy Alone Versus Neoadjuvant Chemotherapy With Folfirinox Regimen Followed by Preoperative Chemoradiotherapy for Patients With Resectable Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2012 (Actual)
Primary Completion Date
September 2019 (Actual)
Study Completion Date
May 2025 (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
National, multi-center, open-label,randomized, 2-arm phase III superiority trial, comparing neoadjuvant chemotherapy (CT) with mFolfirinox followed by preoperative chemoradiotherapy (CRT), versus preoperative CRT in patients with locally advanced rectal cancer.
Detailed Description
Methodology This is a biomedical research, national, multicenter, open-label randomized, 2-arm phase III superiority trial, comparing neoadjuvant CT with mFolfirinox then preoperative CRT, versus immediate preoperative CRT, in patients with locally advanced rectal cancer Randomized Phase III study with stopping rules Stratification : center, gender, tumor location in the rectum (<6 cm from anal verge versus ≥6 cm), initial stage (cT3 vs cT4, and cN0 vs cN+)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of the Rectum
Keywords
rectum, cancer, locally advanced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
461 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A : Radiotherapy + capecitabine
Arm Type
Active Comparator
Arm Description
Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.
Arm Title
Arm B : Chemotherapy then radiochemotherapy
Arm Type
Experimental
Arm Description
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): oxaliplatin: 85 mg/m² in 2 hours at D1 irinotecan: 180 mg/m² in 90 min at D1 folinic acid: 400 mg/m² simultaneously in 2 hours at D1 during the irinotecan infusion 5-fluorouracil (5-FU): 2400 mg/m² continuous infusion during 48 hours (1200 mg/m² at D1 and D2), every 14 days during 2 months (4 cycles). Then followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention Type
Drug
Intervention Name(s)
mFolfirinox
Intervention Description
Investigational arm: Neoadjuvant chemotherapy mFolfirinox, 4 cycles: oxaliplatin: 85 mg/m² in 2 hours at D1 irinotecan: 180 mg/m² in 90 min at D1 folinic acid: 400 mg/m² simultaneously in 2 hours at D1 during the irinotecan infusion 5-FU: 2400 mg/m² continuous infusion during 48 hours (1200 mg/m² at D1 and D2), every 14 days during 2 months (4 cycles), then CRT (50 Gy (2 Gy/session, 25 fractions) + capecitabine 800 mg/m² twice a day 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, and 4 months of adjuvant CT depending on the center's choice.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy 50 Gy
Intervention Description
5 radiations per week of 2 Gy for 5 weeks
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
1600 mg/m² (800 mg/m² twice daily) for 5 weeks
Intervention Type
Procedure
Intervention Name(s)
TME surgery
Intervention Type
Drug
Intervention Name(s)
mFolfox6 or capecitabine
Intervention Description
oxaliplatine 85 mg/m² (day 1 of cycle; perfusion in 2h), folinic acid 400 mg/m² (day 1 of cycle perfusion in 2h), 5-FU (bolus 400 mg/m² in 10 min and 2400 mg/m² perfusion continuous 46h). Arm A - 12 cycles ; Arm B - 6 cycles OR Capecitabine 2500 mg/m²/day (Each cycle consists of 1250 mg/m² twice daily for D1-14 then pause therapeutic from D15-21). Arm A - 8 cycles; Arm B 4 cycles.
Primary Outcome Measure Information:
Title
disease-free survival
Description
To compare the 3-year disease-free survival between the investigational arm and the control arm.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Overall survival will be defined as the time from randomisation to the time of occurrence of the first death regardless to its cause. Patients alive at the time of analysis will be censored at the date of the last follow up.
Time Frame
7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven rectal adenocarcinoma Stages cT3 with risk of local recurrence or cT4, M0 and for which a multidisciplinary meeting recommend preoperative CRT Resectable tumor, or considered as potentially resectable after CRT No distant metastases Patient eligible for surgery Patient aged from 18 to 75 years World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0/2. No heart failure or coronary heart disease symptoms (even controlled). No peripheral neuropathy > grade 1 No prior radiotherapy of the pelvis for any reason and no previous CT No major comorbidity that may preclude the delivery of treatment and no active infection (HIV or chronic hepatitis B or C). Adequate contraception in fertile patients. Adequate hematologic function Adequate hepatic function Signed written informed consent Exclusion Criteria: Metastatic disease Unresectable rectal cancer, including prostatic involvement or extension to pelvic floor muscles Contraindication to 5-FU, or to oxaliplatin or to irinotecan, including Gilbert disease or genotype UGT1A1 Medical history of chronic diarrhea or inflammatory disease of the colon or rectum Medical history of angina pectoris or myocardial infarction Progressive active infection or any other severe medical condition that could jeopardize treatment administration Other concomitant cancer, or medical history of cancer other than treated in situ cervical carcinoma or basocellular carcinoma or spinocellular carcinoma Patient included in another clinical trial testing an investigational agent. Pregnant or breast-feeding woman. Persons deprived of liberty or under guardianship or incapable of giving consent Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry CONROY, PROF
Organizational Affiliation
centre Alexis Vautrin les Nancy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre hospitalier Universitaire d'Amiens
City
Amiens
Country
France
Facility Name
ICO - Site Paul Papin
City
Angers
Country
France
Facility Name
Centre hospitalier d'Auxerre
City
Auxerre
Country
France
Facility Name
Centre Hospitalier de Beauvais
City
Beauvais
Country
France
Facility Name
Institut de Cancérologie de Franche Comté
City
Besancon
Country
France
Facility Name
Centre Hospitalier de Blois
City
Blois
Country
France
Facility Name
Hopital Avicenne
City
Bobigny
Country
France
Facility Name
Clinique Tivoli
City
Bordeaux
Country
France
Facility Name
Hopital Saint Andre
City
Bordeaux
Country
France
Facility Name
Institut Bergonie
City
Bordeaux
Country
France
Facility Name
Centre Francois Baclesse
City
Caen
Country
France
Facility Name
Chd de La Roche Sur Yon - Les Oudairies
City
La Roche-sur-yon
Country
France
Facility Name
Centre Bourgogne
City
Lille
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
Country
France
Facility Name
Hopital Prive Jean Mermoz
City
Lyon
Country
France
Facility Name
Ap Hm - Hopital de La Timone - Adultes
City
Marseille
Country
France
Facility Name
Institut de Cancérologie de Franche Comté
City
Montbeliard
Country
France
Facility Name
Centre Azuréen de cancérologie
City
Mougins
Country
France
Facility Name
Hopital Emile Muller
City
Mulhouse
Country
France
Facility Name
centre Alexis Vautrin
City
Nancy
Country
France
Facility Name
Polyclinique de Gentilly
City
Nancy
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
Groupe Hospitalier La Pitie-Salpetriere
City
Paris
Country
France
Facility Name
Institut Mutualiste Montsouris
City
Paris
Country
France
Facility Name
Hopital Haut Leveque
City
Pessac
Country
France
Facility Name
Centre Hospitalier Regional D'Annecy
City
Pringy
Country
France
Facility Name
Hopital Robert Debre
City
Reims
Country
France
Facility Name
Institut Jean Godinot
City
Reims
Country
France
Facility Name
Clinique Armoricaine de Radiologie
City
Saint-brieuc
Country
France
Facility Name
Hopital Saint Gregoire
City
Saint-gregoire
Country
France
Facility Name
Clinique Mutualiste de L'Estuaire
City
Saint-nazaire
Country
France
Facility Name
Centre Hospitalier de la Réunion - Site du GHSR
City
Saint-pierre
Country
France
Facility Name
ICO - Site René Gauducheau
City
St Herblain
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
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.
Citations:
PubMed Identifier
33862000
Citation
Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.
Results Reference
result
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/33862000/
Description
Lancet Oncology 2021 Apr 13: publication of results

Learn more about this trial

Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer

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