Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 218
- Locations
- 29
- Primary Endpoint
- Rate of organ preservation and absence of stoma
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Rectal adenocarcinoma
- •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
- •Effective contraception during the study
- •Patient and doctor have signed informed consent
Exclusion Criteria
- •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
Arms & Interventions
Chemotherapy and Radiochemotherapy
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)
Intervention: Rectal excision in bad responders (Procedure)
Chemotherapy and Radiochemotherapy
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)
Intervention: Neoadjuvant chemotherapy Folfirinox, 4 cycles (Drug)
Chemotherapy and Radiochemotherapy
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)
Intervention: 50 Gy, 2 Gy/session; 25 fractions (Radiation)
Chemotherapy and Radiochemotherapy
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)
Intervention: Local excision in good responders (Procedure)
Radiochemotherapy
Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
Intervention: 50 Gy, 2 Gy/session; 25 fractions (Radiation)
Radiochemotherapy
Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
Intervention: Local excision in good responders (Procedure)
Radiochemotherapy
Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
Intervention: Rectal excision in bad responders (Procedure)
Chemotherapy and Radiochemotherapy
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)
Intervention: Capecitabine (Drug)
Radiochemotherapy
Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
Intervention: Capecitabine (Drug)
Outcomes
Primary Outcomes
Rate of organ preservation and absence of stoma
Time Frame: 1 year after surgery
Number of patients with organ preservation and absence of stoma at 1 year after surgery
Secondary Outcomes
- Tolerance to treatment(From beginning of neoadjuvant treatment until 1 year after surgery)
- Surgical morbidity(From surgery until 1 year of follow-up)
- Rate of clinical complete response(At 8 weeks after neoadjuvant treatment)
- Correlation between radiological (radiomic analysis) and pathologic response(Between 8 to 10 weeks after neoadjuvant treatment)
- Local recurrence(From surgery until 3 years of follow-up)
- Compliance to treatment(From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment)
- Correlation between radiological and clinical response(Between 8 to 10 weeks after neoadjuvant treatment)
- Quality of life(From randomization until 1 year after surgery)
- Overall survival(From surgery until 3 years of follow-up)
- Rate of radiological response(At 8 weeks after neoadjuvant treatment)
- Rate of complete pathologic response(At surgery, expected average 10 weeks after neoadjuvant treatment)
- Rate of curative surgery(At surgery, expected average 10 weeks after neoadjuvant treatment)
- Disease-free survival(From surgery until 3 years of follow-up)