We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00865189
First Posted: March 19, 2009
Last Update Posted: August 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
March 18, 2009
March 19, 2009
April 13, 2017
August 4, 2017
August 4, 2017
October 23, 2007
March 23, 2016   (Final data collection date for primary outcome measure)
Percentage of Participants With Tumor Sterilization Defined by ypT0-N0 [ Time Frame: 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.
Rate of sterilisation of tumoral specimen: YpT0-N0 [ Time Frame: After surgery (6-8 weeks after chemoradiation) ]
Complete list of historical versions of study NCT00865189 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Tumor Down-Staging (ypT0-pT2) [ Time Frame: 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 [ Time Frame: 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).
  • Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death [ Time Frame: Baseline up to approximately 6 years ]
  • Disease-Free Survival (DFS) [ 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) ]
    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.
  • Percentage of Participants Who Died [ Time Frame: Baseline up to approximately 6 years ]
  • Overall Survival [ Time Frame: 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.
  • 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 [ Time Frame: 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.
Efficacy: Compliance, pathological tumor downstaging rate, recurrence rates, disease free survival, overall survival. Safety: AEs, SAEs, lab parameters, post-operative complications. [ Time Frame: Efficacy:event driven (throughout study) Safety:at each clinic visit throughout study ]
Not Provided
Not Provided
 
A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer
Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study
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).
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Rectal Cancer
  • Drug: Bevacizumab
    Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
    Other Name: Avastin
  • Drug: Oxaliplatin
    Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m^2) as a 2-hour IV infusion.
  • Drug: Folinic Acid
    Folinic acid will be administered at a dose of 200 mg/m^2 as a 2-hour infusion.
  • Drug: 5-fluorouracil
    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.
  • Radiation: Preoperative Radiotherapy
    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.
  • Procedure: Surgery
    Radical rectal excision based on the TME technique.
  • Experimental: Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
    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.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Oxaliplatin
    • Drug: Folinic Acid
    • Drug: 5-fluorouracil
    • Radiation: Preoperative Radiotherapy
    • Procedure: Surgery
  • Experimental: Arm B (Bevacizumab, Chemoradiotherapy)
    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:
    • Drug: Bevacizumab
    • Drug: 5-fluorouracil
    • Radiation: Preoperative Radiotherapy
    • Procedure: Surgery
Borg C, André T, Mantion G, Boudghène 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):2205-10. doi: 10.1093/annonc/mdu377. Epub 2014 Aug 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
March 23, 2016
March 23, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • histologically confirmed locally advanced rectal cancer;
  • measurable disease;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Exclusion Criteria:

  • 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.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France
 
 
NCT00865189
ML19202
2006-003472-35 ( EudraCT Number )
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Chair: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP