Rectal Cancer
Conditions
Keywords
Organ preservation, Local excision, Radiochemotherapy, Neoadjuvant chemotherapy, Folfirinox, Tumour response
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.
Interventions
DRUGNeoadjuvant 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
RADIATION50 Gy, 2 Gy/session; 25 fractions
Radiochemotherapy 5 weeks
PROCEDURELocal 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.
PROCEDURERectal excision in bad responders
DRUGCapecitabine
1600 mg/m2 daily 5 days/7
Sponsors
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of organ preservation and absence of stoma | 1 year after surgery | Number of patients with organ preservation and absence of stoma at 1 year after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compliance to treatment | From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment | Number of patients receiving full neoadjuvent treatment and the allocated surgery |
| Tolerance to treatment | From beginning of neoadjuvant treatment until 1 year after surgery | Number of patients with adverse events |
| Rate of clinical complete response | At 8 weeks after neoadjuvant treatment | To determine the rate of grade 1 : no tumor at digital examination |
| Rate of radiological response | At 8 weeks after neoadjuvant treatment | To determine the rate of tumor ≤ 2 cm with TRG1-3 at MRI |
| Rate of complete pathologic response | At surgery, expected average 10 weeks after neoadjuvant treatment | To determine the rate of ypT0 |
| Correlation between radiological and clinical response | Between 8 to 10 weeks after neoadjuvant treatment | To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and clinical response (grade 1) |
| Correlation between radiological (radiomic analysis) and pathologic response | Between 8 to 10 weeks after neoadjuvant treatment | To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and pathological response (ypT0) |
| Rate of curative surgery | At surgery, expected average 10 weeks after neoadjuvant treatment | To determine the rate of R0 resection |
| Surgical morbidity | From surgery until 1 year of follow-up | To analyse the cumulative Clavien-Dindo at 1 year |
| Quality of life | From randomization until 1 year after surgery | To examine score of questionnaires : QLQ CR-30, QLQ CR-29 |
| Local recurrence | From surgery until 3 years of follow-up | To determine the rate of local recurrence at 3 years |
| Overall survival | From surgery until 3 years of follow-up | To determine the rate of overall survival at 3 years |
| Disease-free survival | From surgery until 3 years of follow-up | To determine the rate of disease-free survival at 3 years |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORChristophe LAURENT, Prof.
University Hospital Bordeaux, France
Outcome results
None listed