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

Rectal Cancer Clinical Trial

— GRECCAR12  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02514278
• Other study ID #: CHUBX 2014/33
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 28, 2016
• Est. completion date: June 2024

Study information

• Verified date: March 2024
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 218
• Est. completion date: June 2024
• Est. primary completion date: June 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• 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

Radiation:
• 50 Gy, 2 Gy/session; 25 fractions
Radiochemotherapy 5 weeks

Procedure:
• Local excision in good responders
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.
• Rectal excision in bad responders

Drug:
• Capecitabine
1600 mg/m2 daily 5 days/7

Locations

Country	Name	City	State
France	Service de Chirurgie Digestive, CHU Amiens Picardie	Amiens
France	Service de Chirurgie Digestive, CHU de Besançon	Besançon
France	Service de Chirurgie Digestive, Hôpital Haut-Lévêque - CHU de Bordeaux	Bordeaux
France	Service de Chirurgie Digestive, Institut Bergonié	Bordeaux
France	Service de Chirurgie Digestive, CHU Estaing - CHRU Clermont Ferrand	Clermont-Ferrand
France	Service de Chirurgie Digestive, Hôpital Beaujon - APHP	Clichy
France	Service de Chirurgie Digestive, Centre Georges François Leclerc - Dijon	Dijon
France	Service de Chirurgie Digestive, Hôpital Albert Michallon - CHU de Grenoble	La Tronche
France	Service de Chirurgie Digestive, Centre Oscar Lambret - Lille	Lille
France	Service de Chirurgie Digestive, Centre Léon Bérard - Lyon	Lyon
France	Service de Chirurgie Digestive, Hôpital Lyon Sud - CHU Lyon	Lyon
France	Service de Chirurgie Digestive, CHU de la Timone - Marseille	Marseille
France	Service de Chirurgie Digestive, Institut Paoli Calmette - Marseille	Marseille
France	Service de Chirurgie Digestives, Hôpital Européen de Marseille	Marseille
France	Service de Chirurgie Digestive, Institut du Cancer de Montpellier	Montpellier
France	Service d'Oncologie et Radiothérapie, Centre Azuréen de Cancérologie	Mougins
France	Service de Chirurgie Digestive,Institut de Cancérologie de Lorraine	Nancy
France	Service de Chirurgie Digestive, Hôtel Dieu - CHU de Nantes	Nantes
France	Service de Chirurgie Digestive, CHU Carémeau - Nîmes	Nîmes
France	GH Paris Saint Joseph	Paris
France	Service de Chirurgie Digestive et Oncologique, Hôpital Bicêtre - APHP	Paris
France	Service de Chirurgie Digestive, Hôpital les Diaconnesses	Paris
France	Service de Chirurgie Digestive, Hôpital Saint-Antoine - APHP	Paris
France	Service de Chirurgie Digestive, Hôpital Saint-Louis - APHP Paris	Paris
France	Service de Chirurgie Digestive, Hôpital Pontchaillou - CHU Rennes	Rennes
France	Service de Chirurgie Digestive, Hôpital Charles Nicolle - CHU de Rouen	Rouen
France	Service de Chirurgie Digestive, Hôpital Purpan - CHU de Toulouse	Toulouse
France	Service de chirurgie digestive, CHRU de Nancy -Hôpital de Brabois	Vandœuvre-lès-Nancy
France	Département de chirurgie digestive, Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Compliance to treatment	Number of patients receiving full neoadjuvent treatment and the allocated surgery	From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment
Secondary	Tolerance to treatment	Number of patients with adverse events	From beginning of neoadjuvant treatment until 1 year after surgery
Secondary	Rate of clinical complete response	To determine the rate of grade 1 : no tumor at digital examination	At 8 weeks after neoadjuvant treatment
Secondary	Rate of radiological response	To determine the rate of tumor = 2 cm with TRG1-3 at MRI	At 8 weeks after neoadjuvant treatment
Secondary	Rate of complete pathologic response	To determine the rate of ypT0	At surgery, expected average 10 weeks after neoadjuvant treatment
Secondary	Correlation between radiological and clinical response	To analyse the correlation between radiological response ( tumor = 2 cm with TRG1-3 at MRI) and clinical response (grade 1)	Between 8 to 10 weeks after neoadjuvant treatment
Secondary	Correlation between radiological (radiomic analysis) and pathologic response	To analyse the correlation between radiological response ( tumor = 2 cm with TRG1-3 at MRI) and pathological response (ypT0)	Between 8 to 10 weeks after neoadjuvant treatment
Secondary	Rate of curative surgery	To determine the rate of R0 resection	At surgery, expected average 10 weeks after neoadjuvant treatment
Secondary	Surgical morbidity	To analyse the cumulative Clavien-Dindo at 1 year	From surgery until 1 year of follow-up
Secondary	Quality of life	To examine score of questionnaires : QLQ CR-30, QLQ CR-29	From randomization until 1 year after surgery
Secondary	Local recurrence	To determine the rate of local recurrence at 3 years	From surgery until 3 years of follow-up
Secondary	Overall survival	To determine the rate of overall survival at 3 years	From surgery until 3 years of follow-up
Secondary	Disease-free survival	To determine the rate of disease-free survival at 3 years	From surgery until 3 years of follow-up