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

NCT ID: NCT00865189

Last Updated: 2017-08-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

91 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-23

Study Completion Date

2016-03-23

Brief Summary

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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).

Detailed Description

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Conditions

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Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

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

Intervention Type DRUG

Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m\^2) as a 2-hour IV infusion.

Folinic Acid

Intervention Type DRUG

Folinic acid will be administered at a dose of 200 mg/m\^2 as a 2-hour infusion.

5-fluorouracil

Intervention Type DRUG

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.

Preoperative Radiotherapy

Intervention Type RADIATION

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.

Surgery

Intervention Type PROCEDURE

Radical rectal excision based on the TME technique.

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.

5-fluorouracil

Intervention Type DRUG

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.

Preoperative Radiotherapy

Intervention Type RADIATION

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.

Surgery

Intervention Type PROCEDURE

Radical rectal excision based on the TME technique.

Interventions

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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.

Intervention Type DRUG

Oxaliplatin

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

Folinic Acid

Folinic acid will be administered at a dose of 200 mg/m\^2 as a 2-hour infusion.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type RADIATION

Surgery

Radical rectal excision based on the TME technique.

Intervention Type PROCEDURE

Other Intervention Names

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Avastin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_CHAIR

Hoffmann-La Roche

Locations

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ICO Paul Papin; Oncologie Medicale.

Angers, , France

Site Status

Angers, , France

Site Status

HOPITAL JEAN MINJOZ; Oncologie

Besançon, , France

Site Status

Besançon, , France

Site Status

Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale

Bordeaux, , France

Site Status

Bordeaux, , France

Site Status

Centre Georges Francois Leclerc; Oncologie 3

Dijon, , France

Site Status

Dijon, , France

Site Status

Hopital Albert Michallon; Radiotherapie

La Tronche, , France

Site Status

La Tronche, , France

Site Status

Centre Oscar Lambret; Radiotherapie

Lille, , France

Site Status

Lille, , France

Site Status

Centre Hospitalier Andre Boulloche; Departement D'Oncologie

Montbéliard, , France

Site Status

Montbéliard, , France

Site Status

Centre Val Aurelle Paul Lamarque; Radiotherapie

Montpellier, , France

Site Status

Montpellier, , France

Site Status

Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE

Nancy, , France

Site Status

Nancy, , France

Site Status

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, , France

Site Status

Nice, , France

Site Status

Hopital Saint Louis; Radiotherapie Oncologie

Paris, , France

Site Status

Paris, , France

Site Status

Ch Pitie Salpetriere; Oncologie Medicale

Paris, , France

Site Status

Paris, , France

Site Status

HOPITAL TENON; Cancerologie Medicale

Paris, , France

Site Status

Paris, , France

Site Status

Ch Lyon Sud; Radiotherapie Sct Jules Courmont

Pierre-Bénite, , France

Site Status

Pierre-Bénite, , France

Site Status

Chu La Miletrie; Radiotherapie

Poitiers, , France

Site Status

Poitiers, , France

Site Status

Ico Rene Gauducheau; Oncologie

Saint-Herblain, , France

Site Status

Saint-Herblain, , France

Site Status

Centre Paul Strauss; Oncologie Medicale

Strasbourg, , France

Site Status

Strasbourg, , France

Site Status

Polyclinique Du Parc; Centre De Hautes Energies

Toulouse, , France

Site Status

Toulouse, , France

Site Status

Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie

Tours, , France

Site Status

Tours, , France

Site Status

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, , France

Site Status

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 25122693 (View on PubMed)

Other Identifiers

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2006-003472-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML19202

Identifier Type: -

Identifier Source: org_study_id

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