Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy

NCT02514278 | Completed Phase 3 DMC

• 2 other identifiers: CHUBX 2014/332015-001100-59
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 29

Brief Summary

Standard treatment of rectal cancer is rectal excision with neoadjuvant radiochemotherapy. A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life. The rational is the fact that 15% of patients have sterilized tumours after radiochemotherapy for T3T4 rectal cancer. The French GRECCAR 2 trial is the first phase III trial investigating this strategy: patients with T2T3 low rectal carcinomas (size ≤4 cm) received 50 Gy with capecitabine and good clinical responders (≤2 cm) were randomized between local and rectal excision. The main findings were: the rate of complete pathologic response was higher after radiochemotherapy for small T2T3 than for T3T4 tumours (40% vs 15% ypT0) and good pathologic responders (ypT0-1) were associated with zero positive mesorectal nodes. The objective of the new trial is to increase the proportion of patients treated with organ preservation by optimizing tumour response. As compared to Folfiri, tritherapy Folfirinox has been shown to enhance the response rate. In patients with colorectal metastases, response rate and R0 resection were twice higher, resulting in improved survival. Folfirinox also increases response and chance of R0 resection rates in initially unresectable colorectal metastases, compared to standard or intensified bi-chemotherapy regimens. Adding two months of neoadjuvant chemotherapy (Folfirinox) before radiochemotherapy, the investigators expect to increase chance of organ preservation rate, as compared to radiochemotherapy alone.

Conditions

Rectal Cancer

Keywords

Organ preservation; Local excision; Radiochemotherapy; Neoadjuvant chemotherapy; Folfirinox; Tumour response

Outcome Measures

Primary Outcomes (1)

• Rate of organ preservation and absence of stoma

  Number of patients with organ preservation and absence of stoma at 1 year after surgery

  1 year after surgery

Secondary Outcomes (13)

• Compliance to treatment

  From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment

• Tolerance to treatment

  From beginning of neoadjuvant treatment until 1 year after surgery

• Rate of clinical complete response

  At 8 weeks after neoadjuvant treatment

• Rate of radiological response

  At 8 weeks after neoadjuvant treatment

• Rate of complete pathologic response

  At surgery, expected average 10 weeks after neoadjuvant treatment

Study Arms (2)

Chemotherapy and Radiochemotherapy

EXPERIMENTAL

Neoadjuvant chemotherapy Folfirinox, 4 cycles: * oxaliplatin: 85 mg/m2 * irinotecan: 180 mg/m² * folinic acid: 400 mg/m2 (DL form) or 200 mg/m2 (L form) * 5FU: 2400 mg/m2 Radiochemotherapy : 2 to 4 weeks after chemotherapy, 5 weeks (50 Gy, 2 Gy/session; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7)

Drug: Neoadjuvant chemotherapy Folfirinox, 4 cycles; Radiation: 50 Gy, 2 Gy/session; 25 fractions; Procedure: Local excision in good responders; Procedure: Rectal excision in bad responders; Drug: Capecitabine

Radiochemotherapy

ACTIVE COMPARATOR

Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)

Radiation: 50 Gy, 2 Gy/session; 25 fractions; Procedure: Local excision in good responders; Procedure: Rectal excision in bad responders; Drug: Capecitabine

Interventions

Neoadjuvant chemotherapy Folfirinox, 4 cycles DRUG

* oxaliplatin: 85 mg/m2 * irinotecan: 180 mg/m² * folinic acid: 400 mg/m2 (DL form) or 200 mg/m2 (L form) * 5FU: 2400 mg/m2

Chemotherapy and Radiochemotherapy

50 Gy, 2 Gy/session; 25 fractions RADIATION

Radiochemotherapy 5 weeks

Chemotherapy and Radiochemotherapy; Radiochemotherapy

Local excision in good responders PROCEDURE

If local excision: * Surveillance if ypT0-1 or ypT2Nx/cN0 (no lymph node at baseline imaging) * Complementary rectal excision if ypT2Nx/cN1, ypT3 or R1.

Chemotherapy and Radiochemotherapy; Radiochemotherapy

Rectal excision in bad responders PROCEDURE

Chemotherapy and Radiochemotherapy; Radiochemotherapy

Capecitabine DRUG

1600 mg/m2 daily 5 days/7

Chemotherapy and Radiochemotherapy; Radiochemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Rectal adenocarcinoma
• cT2T3
• cN0-1 (≤ 3 positive lymph nodes or size ≤8mm)
• Tumour size ≤4 cm
• Location ≤10 cm from the anal verge
• No distant metastasis
• Patient ≥18 years
• ECOG ≤2
• Effective contraception during the study
• Patient and doctor have signed informed consent

You may not qualify if:

• T1 or T4
• Tumour size \>4cm
• N2 (\>3 positive lymph nodes or size \>8mm)
• Tumour \> 10 cm from the anal verge
• Distant metastasis
• Chronic intestinal inflammation and/or bowel obstruction
• Contra indication for chemotherapy and/or radiotherapy
• Previous pelvic radiotherapy or chemotherapy
• Severe renal, hepatic insufficiency (serum creatinine\<30ml/min)
• Peripheral neuropathy \> grade 1
• Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
• Concomitant treatment with millepertuis, yellow fever vaccine, phenytoin or sorivudine (or chemically equivalent)
• Pregnant or breast-feeding woman.
• Persons deprived of liberty or under guardianship
• Impossibility for compliance to follow-up

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (29)

Service de Chirurgie Digestive, CHU Amiens Picardie

Amiens, France

Location

Service de Chirurgie Digestive, CHU de Besançon

Besançon, France

Location

Service de Chirurgie Digestive, Hôpital Haut-Lévêque - CHU de Bordeaux

Bordeaux, France

Location

Service de Chirurgie Digestive, Institut Bergonié

Bordeaux, France

Location

Service de Chirurgie Digestive, CHU Estaing - CHRU Clermont Ferrand

Clermont-Ferrand, France

Location

Service de Chirurgie Digestive, Hôpital Beaujon - APHP

Clichy, France

Location

Service de Chirurgie Digestive, Centre Georges François Leclerc - Dijon

Dijon, France

Location

Service de Chirurgie Digestive, Hôpital Albert Michallon - CHU de Grenoble

La Tronche, France

Location

Service de Chirurgie Digestive, Centre Oscar Lambret - Lille

Lille, France

Location

Service de Chirurgie Digestive, Centre Léon Bérard - Lyon

Lyon, France

Location

Service de Chirurgie Digestive, Hôpital Lyon Sud - CHU Lyon

Lyon, France

Location

Service de Chirurgie Digestive, CHU de la Timone - Marseille

Marseille, France

Location

Service de Chirurgie Digestive, Institut Paoli Calmette - Marseille

Marseille, France

Location

Service de Chirurgie Digestives, Hôpital Européen de Marseille

Marseille, France

Location

Service de Chirurgie Digestive, Institut du Cancer de Montpellier

Montpellier, France

Location

Service d'Oncologie et Radiothérapie, Centre Azuréen de Cancérologie

Mougins, France

Location

Service de Chirurgie Digestive,Institut de Cancérologie de Lorraine

Nancy, France

Location

Service de Chirurgie Digestive, Hôtel Dieu - CHU de Nantes

Nantes, France

Location

Service de Chirurgie Digestive, CHU Carémeau - Nîmes

Nîmes, France

Location

GH Paris Saint Joseph

Paris, France

Location

Service de Chirurgie Digestive et Oncologique, Hôpital Bicêtre - APHP

Paris, France

Location

Service de Chirurgie Digestive, Hôpital les Diaconnesses

Paris, France

Location

Service de Chirurgie Digestive, Hôpital Saint-Antoine - APHP

Paris, France

Location

Service de Chirurgie Digestive, Hôpital Saint-Louis - APHP Paris

Paris, France

Location

Service de Chirurgie Digestive, Hôpital Pontchaillou - CHU Rennes

Rennes, France

Location

Service de Chirurgie Digestive, Hôpital Charles Nicolle - CHU de Rouen

Rouen, France

Location

Service de Chirurgie Digestive, Hôpital Purpan - CHU de Toulouse

Toulouse, France

Location

Service de chirurgie digestive, CHRU de Nancy -Hôpital de Brabois

Vandœuvre-lès-Nancy, France

Location

Département de chirurgie digestive, Institut Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Vendrely V, Denost Q, Charleux T, Brouquet A, Huguet F, Rullier E. [Rectal cancer radiotherapy: Therapeutical strategy and perspective]. Cancer Radiother. 2018 Oct;22(6-7):558-563. doi: 10.1016/j.canrad.2018.06.004. Epub 2018 Aug 28. French.

  PMID: 30170787 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Christophe LAURENT, Prof.

  University Hospital Bordeaux, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: August 3, 2015
• Study Start: January 28, 2016
• Primary Completion: June 9, 2022
• Study Completion: June 30, 2024
• Last Updated: May 14, 2026

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (29)