Conditions: Rectal Cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 91
Healthy volunteers: no

Brief summary:
This study will assess the efficacy and safety of two different neoadjuvant treatment approaches including bevacizumab in newly diagnosed participants with high risk locally advanced rectal cancer. Participants will be randomized into one of two treatment arms (Arm A or Arm B).

Detailed description:

Arms:
arm 1: In this arm, participants will undergo 3 phases of treatment. During the Phase 1, participants will receive induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks. The Phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (intravenous \[IV\] infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy \[5-FU + radiotherapy\], with administration of bevacizumab every two weeks \[Cycles 1, 3 and 5\]) followed by a treatment-free interval of 6 to 8 weeks. The Phase 3 will be surgery involving a radical rectal excision using the total mesorectal excision (TME) technique. arm 2: In this arm, participants will receive the Phase 2 and Phase 3 treatments only. The phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy \[5-FU + radiotherapy\], with administration of bevacizumab every two weeks \[Cycles 1, 3 and 5\]) followed by a treatment-free interval of 6 to 8 weeks. The phase 3 will be surgery involving a radical rectal excision using the TME technique.

Interventions: intervention 1: Bevacizumab intervention 2: Oxaliplatin intervention 3: Folinic Acid intervention 4: 5-fluorouracil intervention 5: Preoperative Radiotherapy intervention 6: Surgery
Intervention descriptions: intervention 1: Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes. intervention 2: Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m\^2) as a 2-hour IV infusion. intervention 3: Folinic acid will be administered at a dose of 200 mg/m\^2 as a 2-hour infusion. intervention 4: 5-fluorouracil will be administered at a dose of 400 mg/m\^2 as an IV bolus, then at a dose of 600 mg/m\^2 as a continuous infusion for 22 hours in Phase 1, and will be administered at a dose of 225 mg/m\^2 as a 24-hour infusion, 5 days a week, for 5 weeks in Phase 2. intervention 5: Radiotherapy will be delivered in fraction of 1.8 gray per day (Gy/day), 5 days a week for 5 weeks, i.e., a total dose of 45 Gy will be administered in 25 fractions over a period of 33 days. intervention 6: Radical rectal excision based on the TME technique.

Protocol document: