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

Primary Purpose

Rectal Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Bevacizumab
Oxaliplatin
Folinic Acid
5-fluorouracil
Preoperative Radiotherapy
Surgery
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • ICO Paul Papin; Oncologie Medicale.
  • HOPITAL JEAN MINJOZ; Oncologie
  • Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
  • Centre Georges Francois Leclerc; Oncologie 3
  • Hopital Albert Michallon; Radiotherapie
  • Centre Oscar Lambret; Radiotherapie
  • Centre Hospitalier Andre Boulloche; Departement D'Oncologie
  • Centre Val Aurelle Paul Lamarque; Radiotherapie
  • Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
  • Centre Antoine Lacassagne; Hopital De Jour A2
  • Hopital Saint Louis; Radiotherapie Oncologie
  • Ch Pitie Salpetriere; Oncologie Medicale
  • HOPITAL TENON; Cancerologie Medicale
  • Ch Lyon Sud; Radiotherapie Sct Jules Courmont
  • Chu La Miletrie; Radiotherapie
  • Ico Rene Gauducheau; Oncologie
  • Centre Paul Strauss; Oncologie Medicale
  • Polyclinique Du Parc; Centre De Hautes Energies
  • Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
  • Centre Alexis Vautrin; Oncologie Medicale

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)

Arm B (Bevacizumab, Chemoradiotherapy)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
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.
Percentage of Participants Who Died
Overall Survival
The overall survival was defined as the time from the first treatment intake to death from any cause.
Number of Cycles of Induction Chemotherapy
Number of Cycles of Chemotherapy
Number of Cycles of Radiotherapy
Percentage of Participants With Surgery
The surgery involving a radical rectal excision using the TME technique.

Full Information

First Posted
March 18, 2009
Last Updated
July 31, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00865189
Brief Title
A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer
Acronym
INOVA
Official Title
Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 23, 2007 (Actual)
Primary Completion Date
March 23, 2016 (Actual)
Study Completion Date
March 23, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
Arm Type
Experimental
Arm Description
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 Title
Arm B (Bevacizumab, Chemoradiotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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 Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m^2) as a 2-hour IV infusion.
Intervention Type
Drug
Intervention Name(s)
Folinic Acid
Intervention Description
Folinic acid will be administered at a dose of 200 mg/m^2 as a 2-hour infusion.
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
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 Type
Radiation
Intervention Name(s)
Preoperative Radiotherapy
Intervention Description
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 Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Radical rectal excision based on the TME technique.
Primary Outcome Measure Information:
Title
Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Description
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)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
Description
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)
Title
Percentage of Participants With Local and Distant Recurrences
Description
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)
Title
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
Time Frame
Baseline up to approximately 6 years
Title
Disease-Free Survival (DFS)
Description
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)
Title
Percentage of Participants Who Died
Time Frame
Baseline up to approximately 6 years
Title
Overall Survival
Description
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)
Title
Number of Cycles of Induction Chemotherapy
Time Frame
6 cycles (12 weeks; cycle length = 14 days)
Title
Number of Cycles of Chemotherapy
Time Frame
Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Title
Number of Cycles of Radiotherapy
Time Frame
Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Title
Percentage of Participants With Surgery
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
Facility Name
ICO Paul Papin; Oncologie Medicale.
City
Angers
ZIP/Postal Code
49055
Country
France
City
Angers
ZIP/Postal Code
49055
Country
France
Facility Name
HOPITAL JEAN MINJOZ; Oncologie
City
Besancon
ZIP/Postal Code
25030
Country
France
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
City
Bordeaux
ZIP/Postal Code
33075
Country
France
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
Centre Georges Francois Leclerc; Oncologie 3
City
Dijon
ZIP/Postal Code
21079
Country
France
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Hopital Albert Michallon; Radiotherapie
City
La Tronche
ZIP/Postal Code
38700
Country
France
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Centre Oscar Lambret; Radiotherapie
City
Lille
ZIP/Postal Code
59020
Country
France
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Hospitalier Andre Boulloche; Departement D'Oncologie
City
Montbeliard
ZIP/Postal Code
25209
Country
France
City
Montbeliard
ZIP/Postal Code
25209
Country
France
Facility Name
Centre Val Aurelle Paul Lamarque; Radiotherapie
City
Montpellier
ZIP/Postal Code
34928
Country
France
City
Montpellier
ZIP/Postal Code
34928
Country
France
Facility Name
Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
City
Nancy
ZIP/Postal Code
54100
Country
France
City
Nancy
ZIP/Postal Code
54100
Country
France
Facility Name
Centre Antoine Lacassagne; Hopital De Jour A2
City
Nice
ZIP/Postal Code
06189
Country
France
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Hopital Saint Louis; Radiotherapie Oncologie
City
Paris
ZIP/Postal Code
75475
Country
France
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Ch Pitie Salpetriere; Oncologie Medicale
City
Paris
ZIP/Postal Code
75651
Country
France
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
HOPITAL TENON; Cancerologie Medicale
City
Paris
ZIP/Postal Code
75970
Country
France
City
Paris
ZIP/Postal Code
75970
Country
France
Facility Name
Ch Lyon Sud; Radiotherapie Sct Jules Courmont
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Chu La Miletrie; Radiotherapie
City
Poitiers
ZIP/Postal Code
86021
Country
France
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Ico Rene Gauducheau; Oncologie
City
Saint Herblain
ZIP/Postal Code
44805
Country
France
City
Saint Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Centre Paul Strauss; Oncologie Medicale
City
Strasbourg
ZIP/Postal Code
67065
Country
France
City
Strasbourg
ZIP/Postal Code
67065
Country
France
Facility Name
Polyclinique Du Parc; Centre De Hautes Energies
City
Toulouse
ZIP/Postal Code
31078
Country
France
City
Toulouse
ZIP/Postal Code
31078
Country
France
Facility Name
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
City
Tours
ZIP/Postal Code
37044
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Centre Alexis Vautrin; Oncologie Medicale
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25122693
Citation
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.
Results Reference
derived

Learn more about this trial

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

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