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

NCT ID: NCT01804790

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 461 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2023-07-01

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+)

Conditions

Cancer of the Rectum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A : Radiotherapy + capecitabine

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.

Group Type: ACTIVE_COMPARATOR

Radiotherapy 50 Gy

Intervention Type: RADIATION

5 radiations per week of 2 Gy for 5 weeks

Capecitabine

Intervention Type: DRUG

1600 mg/m² (800 mg/m² twice daily) for 5 weeks

TME surgery

Intervention Type: PROCEDURE

mFolfox6 or capecitabine

Intervention Type: DRUG

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.

Arm B : Chemotherapy then radiochemotherapy

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.

Group Type: EXPERIMENTAL

mFolfirinox

Intervention Type: DRUG

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.

Radiotherapy 50 Gy

Intervention Type: RADIATION

5 radiations per week of 2 Gy for 5 weeks

Capecitabine

Intervention Type: DRUG

1600 mg/m² (800 mg/m² twice daily) for 5 weeks

TME surgery

Intervention Type: PROCEDURE

mFolfox6 or capecitabine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Radiotherapy 50 Gy

5 radiations per week of 2 Gy for 5 weeks

Intervention Type: RADIATION

Capecitabine

1600 mg/m² (800 mg/m² twice daily) for 5 weeks

Intervention Type: DRUG

TME surgery

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry CONROY, PROF

Role: PRINCIPAL_INVESTIGATOR

centre Alexis Vautrin les Nancy

Locations

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

Besançon, , 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

Montbéliard, , 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-Grégoire, , France

ICO - Site René Gauducheau

Saint-Herblain, , France

Clinique Mutualiste de L'Estuaire

Saint-Nazaire, , France

Centre Hospitalier de la Réunion - Site du GHSR

Saint-Pierre, , France

Centre Paul Strauss

Strasbourg, , France

Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 33862000 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/33862000/

Lancet Oncology 2021 Apr 13: publication of results

Other Identifiers

2011-004406-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PRODIGE 23 - UCGI 23

Identifier Type: -

Identifier Source: org_study_id