A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer
- Conditions
- Rectal Cancer
- Interventions
- Radiation: Preoperative RadiotherapyProcedure: Surgery
- Registration Number
- NCT00865189
- Lead Sponsor
- Hoffmann-La Roche
- 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
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 91
- histologically confirmed locally advanced rectal cancer;
- measurable disease;
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- prior treatment with bevacizumab;
- prior radiotherapy to pelvic region, or previous cytotoxic chemotherapy;
- previous history of malignancy (other than basal and squamous cell cancer of the skin, or in situ cancer of the cervix);
- history or evidence of central nervous system (CNS) disease;
- clinically significant cardiovascular disease;
- chronic treatment with high dose aspirin (more than [>] 325 milligrams per day [mg/day]) or non-steroidal anti-inflammatory drugs.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Preoperative Radiotherapy 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 A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Surgery 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 B (Bevacizumab, Chemoradiotherapy) Preoperative Radiotherapy 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. Arm B (Bevacizumab, Chemoradiotherapy) Surgery 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. Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Bevacizumab 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 A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Oxaliplatin 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 A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) Folinic Acid 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 A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy) 5-fluorouracil 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 B (Bevacizumab, Chemoradiotherapy) Bevacizumab 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. Arm B (Bevacizumab, Chemoradiotherapy) 5-fluorouracil 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Tumor Sterilization Defined by ypT0-N0 After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment) 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Died Baseline up to approximately 6 years Number of Cycles of Chemotherapy Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7 Percentage of Participants With Surgery Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment The surgery involving a radical rectal excision using the TME technique.
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death Baseline up to approximately 6 years Overall Survival From the first treatment administration to the date of death (up to approximately 6 years) The overall survival was defined as the time from the first treatment intake to death from any cause.
Percentage of Participants With Tumor Down-Staging (ypT0-pT2) After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment) 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.
Percentage of Participants With Local and Distant Recurrences After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment) The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).
Disease-Free Survival (DFS) 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) 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.
Number of Cycles of Induction Chemotherapy 6 cycles (12 weeks; cycle length = 14 days) Number of Cycles of Radiotherapy Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Trial Locations
- Locations (20)
ICO Paul Papin; Oncologie Medicale.
🇫🇷Angers, France
HOPITAL JEAN MINJOZ; Oncologie
🇫🇷Besancon, France
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
Centre Oscar Lambret; Radiotherapie
🇫🇷Lille, France
Hopital Albert Michallon; Radiotherapie
🇫🇷La Tronche, France
Centre Hospitalier Andre Boulloche; Departement D'Oncologie
🇫🇷Montbeliard, France
Centre Val Aurelle Paul Lamarque; Radiotherapie
🇫🇷Montpellier, France
Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
🇫🇷Nancy, France
Centre Antoine Lacassagne; Hopital De Jour A2
🇫🇷Nice, France
Hopital Saint Louis; Radiotherapie Oncologie
🇫🇷Paris, France
Ch Pitie Salpetriere; Oncologie Medicale
🇫🇷Paris, France
HOPITAL TENON; Cancerologie Medicale
🇫🇷Paris, France
Ch Lyon Sud; Radiotherapie Sct Jules Courmont
🇫🇷Pierre Benite, France
Chu La Miletrie; Radiotherapie
🇫🇷Poitiers, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Centre Paul Strauss; Oncologie Medicale
🇫🇷Strasbourg, France
Polyclinique Du Parc; Centre De Hautes Energies
🇫🇷Toulouse, France
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
🇫🇷Tours, France
Centre Alexis Vautrin; Oncologie Medicale
🇫🇷Vandoeuvre Les Nancy, France