A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer
INOVA
Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study
2 other identifiers
interventional
91
1 country
40
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2007
Longer than P75 for phase_2
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 23, 2007
CompletedFirst Submitted
Initial submission to the registry
March 18, 2009
CompletedFirst Posted
Study publicly available on registry
March 19, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 23, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 23, 2016
CompletedResults Posted
Study results publicly available
August 4, 2017
CompletedAugust 4, 2017
July 1, 2017
8.4 years
March 18, 2009
April 13, 2017
July 31, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
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.
After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Secondary Outcomes (10)
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)
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)
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
Baseline up to approximately 6 years
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)
Percentage of Participants Who Died
Baseline up to approximately 6 years
- +5 more secondary outcomes
Study Arms (2)
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
EXPERIMENTALIn 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)
EXPERIMENTALIn 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
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.
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.
Eligibility Criteria
You may qualify if:
- histologically confirmed locally advanced rectal cancer;
- measurable disease;
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (40)
ICO Paul Papin; Oncologie Medicale.
Angers, 49055, France
Unknown Facility
Angers, 49055, France
HOPITAL JEAN MINJOZ; Oncologie
Besançon, 25030, France
Unknown Facility
Besançon, 25030, France
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
Bordeaux, 33075, France
Unknown Facility
Bordeaux, 33075, France
Centre Georges Francois Leclerc; Oncologie 3
Dijon, 21079, France
Unknown Facility
Dijon, 21079, France
Hopital Albert Michallon; Radiotherapie
La Tronche, 38700, France
Unknown Facility
La Tronche, 38700, France
Centre Oscar Lambret; Radiotherapie
Lille, 59020, France
Unknown Facility
Lille, 59020, France
Centre Hospitalier Andre Boulloche; Departement D'Oncologie
Montbéliard, 25209, France
Unknown Facility
Montbéliard, 25209, France
Centre Val Aurelle Paul Lamarque; Radiotherapie
Montpellier, 34928, France
Unknown Facility
Montpellier, 34928, France
Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
Nancy, 54100, France
Unknown Facility
Nancy, 54100, France
Centre Antoine Lacassagne; Hopital De Jour A2
Nice, 06189, France
Unknown Facility
Nice, 06189, France
Hopital Saint Louis; Radiotherapie Oncologie
Paris, 75475, France
Unknown Facility
Paris, 75475, France
Ch Pitie Salpetriere; Oncologie Medicale
Paris, 75651, France
Unknown Facility
Paris, 75651, France
HOPITAL TENON; Cancerologie Medicale
Paris, 75970, France
Unknown Facility
Paris, 75970, France
Ch Lyon Sud; Radiotherapie Sct Jules Courmont
Pierre-Bénite, 69495, France
Unknown Facility
Pierre-Bénite, 69495, France
Chu La Miletrie; Radiotherapie
Poitiers, 86021, France
Unknown Facility
Poitiers, 86021, France
Ico Rene Gauducheau; Oncologie
Saint-Herblain, 44805, France
Unknown Facility
Saint-Herblain, 44805, France
Centre Paul Strauss; Oncologie Medicale
Strasbourg, 67065, France
Unknown Facility
Strasbourg, 67065, France
Polyclinique Du Parc; Centre De Hautes Energies
Toulouse, 31078, France
Unknown Facility
Toulouse, 31078, France
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
Tours, 37044, France
Unknown Facility
Tours, 37044, France
Centre Alexis Vautrin; Oncologie Medicale
Vandœuvre-lès-Nancy, 54511, France
Unknown Facility
Vandœuvre-lès-Nancy, 54511, France
Related Publications (1)
Borg C, Andre T, Mantion G, Boudghene F, Mornex F, Maingon P, Adenis A, Azria D, Piutti M, Morsli O, Bosset JF. Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. Ann Oncol. 2014 Nov;25(11):2205-2210. doi: 10.1093/annonc/mdu377. Epub 2014 Aug 13.
PMID: 25122693DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY CHAIR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 18, 2009
First Posted
March 19, 2009
Study Start
October 23, 2007
Primary Completion
March 23, 2016
Study Completion
March 23, 2016
Last Updated
August 4, 2017
Results First Posted
August 4, 2017
Record last verified: 2017-07