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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
218
* 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 5 weeks
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.
1600 mg/m2 daily 5 days/7
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
Rate of organ preservation and absence of stoma
Number of patients with organ preservation and absence of stoma at 1 year after surgery
Time frame: 1 year after surgery
Compliance to treatment
Number of patients receiving full neoadjuvent treatment and the allocated surgery
Time frame: From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment
Tolerance to treatment
Number of patients with adverse events
Time frame: From beginning of neoadjuvant treatment until 1 year after surgery
Rate of clinical complete response
To determine the rate of grade 1 : no tumor at digital examination
Time frame: At 8 weeks after neoadjuvant treatment
Rate of radiological response
To determine the rate of tumor ≤ 2 cm with TRG1-3 at MRI
Time frame: At 8 weeks after neoadjuvant treatment
Rate of complete pathologic response
To determine the rate of ypT0
Time frame: At surgery, expected average 10 weeks after neoadjuvant treatment
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)
Time frame: Between 8 to 10 weeks after neoadjuvant treatment
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)
Time frame: Between 8 to 10 weeks after neoadjuvant treatment
Rate of curative surgery
To determine the rate of R0 resection
Time frame: At surgery, expected average 10 weeks after neoadjuvant treatment
Surgical morbidity
To analyse the cumulative Clavien-Dindo at 1 year
Time frame: From surgery until 1 year of follow-up
Quality of life
To examine score of questionnaires : QLQ CR-30, QLQ CR-29
Time frame: From randomization until 1 year after surgery
Local recurrence
To determine the rate of local recurrence at 3 years
Time frame: From surgery until 3 years of follow-up
Overall survival
To determine the rate of overall survival at 3 years
Time frame: From surgery until 3 years of follow-up
Disease-free survival
To determine the rate of disease-free survival at 3 years
Time frame: From surgery until 3 years of follow-up
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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
...and 19 more locations