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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
  Purpose
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).

Condition Intervention Phase
Rectal Cancer Drug: Bevacizumab Drug: Oxaliplatin Drug: Folinic Acid Drug: 5-fluorouracil Radiation: Preoperative Radiotherapy Procedure: Surgery Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 91
Actual Study Start Date: October 23, 2007
Study Completion Date: March 23, 2016
Primary Completion Date: March 23, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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: 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00865189


Locations
France
ICO Paul Papin; Oncologie Medicale.
Angers, France, 49055
Angers, France, 49055
HOPITAL JEAN MINJOZ; Oncologie
Besancon, France, 25030
Besancon, France, 25030
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
Bordeaux, France, 33075
Bordeaux, France, 33075
Centre Georges Francois Leclerc; Oncologie 3
Dijon, France, 21079
Dijon, France, 21079
Hopital Albert Michallon; Radiotherapie
La Tronche, France, 38700
La Tronche, France, 38700
Centre Oscar Lambret; Radiotherapie
Lille, France, 59020
Lille, France, 59020
Centre Hospitalier Andre Boulloche; Departement D'Oncologie
Montbeliard, France, 25209
Montbeliard, France, 25209
Centre Val Aurelle Paul Lamarque; Radiotherapie
Montpellier, France, 34928
Montpellier, France, 34928
Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
Nancy, France, 54100
Nancy, France, 54100
Centre Antoine Lacassagne; Hopital De Jour A2
Nice, France, 06189
Nice, France, 06189
Hopital Saint Louis; Radiotherapie Oncologie
Paris, France, 75475
Paris, France, 75475
Ch Pitie Salpetriere; Oncologie Medicale
Paris, France, 75651
Paris, France, 75651
HOPITAL TENON; Cancerologie Medicale
Paris, France, 75970
Paris, France, 75970
Ch Lyon Sud; Radiotherapie Sct Jules Courmont
Pierre Benite, France, 69495
Pierre Benite, France, 69495
Chu La Miletrie; Radiotherapie
Poitiers, France, 86021
Poitiers, France, 86021
Ico Rene Gauducheau; Oncologie
Saint Herblain, France, 44805
Saint Herblain, France, 44805
Centre Paul Strauss; Oncologie Medicale
Strasbourg, France, 67065
Strasbourg, France, 67065
Polyclinique Du Parc; Centre De Hautes Energies
Toulouse, France, 31078
Toulouse, France, 31078
Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
Tours, France, 37044
Tours, France, 37044
Centre Alexis Vautrin; Oncologie Medicale
Vandoeuvre Les Nancy, France, 54511
Vandoeuvre Les Nancy, France, 54511
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00865189     History of Changes
Other Study ID Numbers: ML19202
2006-003472-35 ( EudraCT Number )
First Submitted: March 18, 2009
First Posted: March 19, 2009
Results First Submitted: April 13, 2017
Results First Posted: August 4, 2017
Last Update Posted: August 4, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Fluorouracil
Leucovorin
Folic Acid
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents