Clinical trial NCT01481545
Conditions: Rectal Cancer
Keywords: locally advanced high risk preoperative therapy
Sponsor: National Cancer Institute, Naples
Start date: 2006-12-01; Completion date: 2016-12-01
Enrollment: 62 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).

Detailed description:
To determine the pathological complete response (pCR-TRG1) rate in patients treated with 2 different schedule of bevacizumab plus primary chemotherapy and radiotherapy of the pelvic region when optimal surgery is applied.

Bevacizumab will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage with the classical schedule Simon's methods will be used to calculate sample size.Setting a and b errors as 0.05 and 0.20, respectively, and defining as minimum activity of interest (p0) a TRG1 rate=30%. In order to demonstrate a TRG1 rate ≥50% (p1), at least 6 TRG1 on the first 15 patients, and at least 19 TRG1 on a total of 46 patients should be reported in the first and second stage, respectively.

Arms: arm 1: Preoperative radiation therapy and combination chemotherapy plus bevacizumab
Interventions: intervention 1: Radiation therapy intervention 2: Oxaliplatin intervention 3: Raltitrexed intervention 4: levofolinic acid intervention 5: 5-fluorouracil intervention 6: Bevacizumab
Intervention descriptions: intervention 1: Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy intervention 2: 100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) intervention 3: 2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy) intervention 4: 250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) intervention 5: 800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) intervention 6: will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)

Protocol documents: