A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)
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| ClinicalTrials.gov Identifier: NCT00865189 |
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Recruitment Status :
Completed
First Posted : March 19, 2009
Results First Posted : August 4, 2017
Last Update Posted : August 4, 2017
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rectal Cancer | Drug: Bevacizumab Drug: Oxaliplatin Drug: Folinic Acid Drug: 5-fluorouracil Radiation: Preoperative Radiotherapy Procedure: Surgery | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 91 participants |
| 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 |
| Actual Study Start Date : | October 23, 2007 |
| Actual Primary Completion Date : | March 23, 2016 |
| Actual Study Completion Date : | March 23, 2016 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Bevacizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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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. |
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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.
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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. |
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.
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| 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.
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
Show 40 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Chair: | Clinical Trials | Hoffmann-La Roche |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT00865189 |
| Other Study ID Numbers: |
ML19202 2006-003472-35 ( EudraCT Number ) |
| First Posted: | March 19, 2009 Key Record Dates |
| Results First Posted: | August 4, 2017 |
| Last Update Posted: | August 4, 2017 |
| Last Verified: | July 2017 |
Additional relevant MeSH terms:
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Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Rectal Diseases Leucovorin Folic Acid Bevacizumab Fluorouracil |
Oxaliplatin Levoleucovorin Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Antidotes |