Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy (GRECCAR12)

University Hospital of Bordeaux

Status and phase: Completed; Phase 3

Conditions: Rectal Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02514278

CHUBX 2014/33

Details and patient eligibility

About

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.

Enrollment: 218 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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218 participants in 2 patient groups

Chemotherapy and Radiochemotherapy

Experimental group

Description:

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)

Treatment:

Procedure: Rectal excision in bad responders

Radiation: 50 Gy, 2 Gy/session; 25 fractions

Drug: Capecitabine

Procedure: Local excision in good responders

Drug: Neoadjuvant chemotherapy Folfirinox, 4 cycles

Radiochemotherapy

Active Comparator group

Description:

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

Treatment:

Procedure: Rectal excision in bad responders

Radiation: 50 Gy, 2 Gy/session; 25 fractions

Drug: Capecitabine

Procedure: Local excision in good responders