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

Cancer of the Rectum Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01804790
• Other study ID #: PRODIGE 23 - UCGI 23
• Secondary ID: 2011-004406-25
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2012
• Est. completion date: May 2025

Study information

• Verified date: August 2023
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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+)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 461
• Est. completion date: May 2025
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cancer of the Rectum
• Rectal Neoplasms

Intervention

Drug:
• mFolfirinox
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.

Radiation:
• Radiotherapy 50 Gy
5 radiations per week of 2 Gy for 5 weeks

Drug:
• Capecitabine
1600 mg/m² (800 mg/m² twice daily) for 5 weeks

Procedure:
• TME surgery

Drug:
• mFolfox6 or capecitabine
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.

Locations

Country	Name	City	State
France	Centre hospitalier Universitaire d'Amiens	Amiens
France	ICO - Site Paul Papin	Angers
France	Centre hospitalier d'Auxerre	Auxerre
France	Centre Hospitalier de Beauvais	Beauvais
France	Institut de Cancérologie de Franche Comté	Besancon
France	Centre Hospitalier de Blois	Blois
France	Hopital Avicenne	Bobigny
France	Clinique Tivoli	Bordeaux
France	Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	Centre Francois Baclesse	Caen
France	Chd de La Roche Sur Yon - Les Oudairies	La Roche-sur-yon
France	Centre Bourgogne	Lille
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	Hopital Prive Jean Mermoz	Lyon
France	Ap Hm - Hopital de La Timone - Adultes	Marseille
France	Institut de Cancérologie de Franche Comté	Montbeliard
France	Centre Azuréen de cancérologie	Mougins
France	Hopital Emile Muller	Mulhouse
France	centre Alexis Vautrin	Nancy
France	Polyclinique de Gentilly	Nancy
France	Centre Antoine Lacassagne	Nice
France	Groupe Hospitalier La Pitie-Salpetriere	Paris
France	Institut Mutualiste Montsouris	Paris
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Regional D'Annecy	Pringy
France	Hopital Robert Debre	Reims
France	Institut Jean Godinot	Reims
France	Clinique Armoricaine de Radiologie	Saint-brieuc
France	Hopital Saint Gregoire	Saint-gregoire
France	Clinique Mutualiste de L'Estuaire	Saint-nazaire
France	Centre Hospitalier de la Réunion - Site du GHSR	Saint-pierre
France	ICO - Site René Gauducheau	St Herblain
France	Centre Paul Strauss	Strasbourg
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

References & Publications (1)

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, G — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival	To compare the 3-year disease-free survival between the investigational arm and the control arm.	3 years
Secondary	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.	7 years

External Links

•   Lancet Oncology 2021 Apr 13: publication of results