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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
91
Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m\^2) as a 2-hour IV infusion.
Folinic acid will be administered at a dose of 200 mg/m\^2 as a 2-hour infusion.
Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Tumor sterilization was defined as the absence of residual tumor cells in the resected specimen including lymph nodes (ypT0-N0). The rate of sterilization of the tumoral specimen was assessed after surgery on the surgical specimen by local review. Analyses were performed for participants who have been operated as defined by the protocol (within the study and TME technique) and for all participants who have been operated. Reported is the percentage of participants with tumor sterilization.
Time frame: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
A participant with a downstaging was defined as a participant with T3 (T describes the size of the original \[primary\] tumor) at inclusion and T2 or T1 or T0 after surgery, or with N+ (N describes lymph nodes involvement) at inclusion and N- after surgery and if T is equal at inclusion and after surgery. The clinical tumor-node-metastasis (cTNM) classification was used at inclusion and the pathological staging tumor and nodes (ypTN) classification after surgery. Reported is the percentage of participants with tumor downstaging of the surgical specimen according to the local review and centralized review.
Time frame: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Percentage of Participants With Local and Distant Recurrences
The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).
Time frame: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
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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.
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.
Radical rectal excision based on the TME technique.
ICO Paul Papin; Oncologie Medicale.
Angers, France
Unnamed facility
Angers, France
HOPITAL JEAN MINJOZ; Oncologie
Besançon, France
Unnamed facility
Besançon, France
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
Bordeaux, France
Unnamed facility
Bordeaux, France
Centre Georges Francois Leclerc; Oncologie 3
Dijon, France
Unnamed facility
Dijon, France
Hopital Albert Michallon; Radiotherapie
La Tronche, France
Unnamed facility
La Tronche, France
...and 30 more locations
Time frame: Baseline up to approximately 6 years
Disease-Free Survival (DFS)
The DFS was defined as the time from the first treatment intake to disease recurrence assessed (second primary cancer, local or distant recurrence, distant metastases) or death from any cause. The DFS was analyzed using Kaplan-Meier method.
Time frame: From first time of the treatment administration to the date of second cancer, local or regional recurrence, distant metastasis or death from any cause (up to approximately 6 years)
Percentage of Participants Who Died
Time frame: Baseline up to approximately 6 years
Overall Survival
The overall survival was defined as the time from the first treatment intake to death from any cause.
Time frame: From the first treatment administration to the date of death (up to approximately 6 years)
Number of Cycles of Induction Chemotherapy
Time frame: 6 cycles (12 weeks; cycle length = 14 days)
Number of Cycles of Chemotherapy
Time frame: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Number of Cycles of Radiotherapy
Time frame: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Percentage of Participants With Surgery
The surgery involving a radical rectal excision using the TME technique.
Time frame: Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment