A Study of Bevacizumab Added to Trastuzumab Plus Docetaxel in the Neoadjuvant Setting in Participants With Early Stage HER2-Positive Breast Cancer

NCT ID: NCT01142778

Last Updated: 2018-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-19
• Study Completion Date: 2017-12-13

Brief Summary

This randomized study will assess the effect of adding bevacizumab to trastuzumab plus docetaxel in neoadjuvant therapy in participants with early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. After 2 cycles of trastuzumab and docetaxel once every 3 weeks, participants with a response (change in standard uptake value [SUV]) of less than (<) 70 percent (%) on Positron Emission Tomography (PET) will be randomized in a 2:1 ratio to receive Cycles 3 to 6 of trastuzumab (6 milligrams per kilogram [mg/kg]) and docetaxel (100 milligrams per square meter [mg/m^2]) with or without bevacizumab (15 mg/kg). Participants with a response of greater than or equal to (>/=) 70% will receive trastuzumab plus docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the treatment perfusion of Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy (starting from 4-8 weeks after surgery during 4-6 weeks, according to site's standard practice) with or without hormonal therapy (mandatory if positive hormone receptors). Participants will be followed for up to 5 years from start of neoadjuvant treatment.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab, Docetaxel, and Bevacizumab

Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of \<70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab at a dose of 15 mg/kg will be administered as IV infusion over 90 minutes from Cycles 3-6 (1 Cycle=21 days).

Docetaxel

Intervention Type: DRUG

Docetaxel at a dose of 100 mg/m\^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days).

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered as a loading dose of 8 mg/kg as IV infusion in Cycle 1, followed by subsequent dose of 6 mg/kg as IV infusion in Cycles 2 to 7, and during additional 11 cycles post surgery (1 Cycle=21 days).

Surgery

Intervention Type: PROCEDURE

All participants will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the study treatment infusion in Cycle 6 (1 Cycle=21 days).

Radiotherapy

Intervention Type: RADIATION

All participants will receive radiotherapy starting about 4 to 8 weeks after surgery, and will last around 4 to 6 weeks as per site's standard practice.

Hormonal Therapy

Intervention Type: DRUG

Participants who are hormone receptors positive, will receive hormonal therapy after completion of radio therapy period as per investigator's discretion and site's standard practice.

Trastuzumab and Docetaxel

Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of \<70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Docetaxel at a dose of 100 mg/m\^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days).

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered as a loading dose of 8 mg/kg as IV infusion in Cycle 1, followed by subsequent dose of 6 mg/kg as IV infusion in Cycles 2 to 7, and during additional 11 cycles post surgery (1 Cycle=21 days).

Surgery

Intervention Type: PROCEDURE

All participants will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the study treatment infusion in Cycle 6 (1 Cycle=21 days).

Radiotherapy

Intervention Type: RADIATION

All participants will receive radiotherapy starting about 4 to 8 weeks after surgery, and will last around 4 to 6 weeks as per site's standard practice.

Hormonal Therapy

Intervention Type: DRUG

Participants who are hormone receptors positive, will receive hormonal therapy after completion of radio therapy period as per investigator's discretion and site's standard practice.

Trastuzumab and Docetaxel (Standard Regimen)

Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of \>/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Docetaxel at a dose of 100 mg/m\^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days).

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered as a loading dose of 8 mg/kg as IV infusion in Cycle 1, followed by subsequent dose of 6 mg/kg as IV infusion in Cycles 2 to 7, and during additional 11 cycles post surgery (1 Cycle=21 days).

Surgery

Intervention Type: PROCEDURE

All participants will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the study treatment infusion in Cycle 6 (1 Cycle=21 days).

Radiotherapy

Intervention Type: RADIATION

All participants will receive radiotherapy starting about 4 to 8 weeks after surgery, and will last around 4 to 6 weeks as per site's standard practice.

Hormonal Therapy

Intervention Type: DRUG

Participants who are hormone receptors positive, will receive hormonal therapy after completion of radio therapy period as per investigator's discretion and site's standard practice.

Interventions

Bevacizumab

Bevacizumab at a dose of 15 mg/kg will be administered as IV infusion over 90 minutes from Cycles 3-6 (1 Cycle=21 days).

Intervention Type: DRUG

Docetaxel

Docetaxel at a dose of 100 mg/m\^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days).

Intervention Type: DRUG

Trastuzumab

Trastuzumab will be administered as a loading dose of 8 mg/kg as IV infusion in Cycle 1, followed by subsequent dose of 6 mg/kg as IV infusion in Cycles 2 to 7, and during additional 11 cycles post surgery (1 Cycle=21 days).

Intervention Type: DRUG

Surgery

All participants will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the study treatment infusion in Cycle 6 (1 Cycle=21 days).

Intervention Type: PROCEDURE

Radiotherapy

All participants will receive radiotherapy starting about 4 to 8 weeks after surgery, and will last around 4 to 6 weeks as per site's standard practice.

Intervention Type: RADIATION

Hormonal Therapy

Participants who are hormone receptors positive, will receive hormonal therapy after completion of radio therapy period as per investigator's discretion and site's standard practice.

Intervention Type: DRUG

Other Intervention Names

Avastin; Taxotere; Herceptin

Eligibility Criteria

Inclusion Criteria

• Participants with early stage HER2-positive breast cancer
• Scheduled to receive neoadjuvant therapy with the objective of conservative surgery
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria

• Participants with partial or total lobular carcinoma
• Participants with inflammatory breast cancer
• Previous treatment with chemotherapy, radiation therapy or hormonal therapy for breast cancer
• Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix) relapsing within the 5 years before study entry or in situ contralateral breast carcinoma

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Centre Radiotherapie Marie Curie

Arras, , France

Centre Hospitalier; Hematologie-Oncologie

Beauvais, , France

Clinique Tivoli; Sce Radiotherapie

Bordeaux, , France

Hopital Augustin Morvan; Federation De Cancerologie

Brest, , France

Centre Jean Perrin; Hopital De Jour

Clermont-Ferrand, , France

Pole Sante Republique;Oncologie Hematologie

Clermont-Ferrand, , France

Centre Georges Francois Leclerc; Oncologie 3

Dijon, , France

Institut Daniel Hollard

Grenoble, , France

Centre Hospitalier Departemental Les Oudairies

La Roche-sur-Yon, , France

Hopital Dupuytren; Oncologie Medicale

Limoges, , France

Centre Leon Berard; Oncologie Genetique

Lyon, , France

Hopital Clinique Claude Bernard; Oncologie Medicale

Metz, , France

Ch De Montlucon; Sce Med Interne Hemato Onco

Montluçon, , France

Institut régional du Cancer Montpellier

Montpellier, , France

Centre D'Oncologie de Gentilly; Oncology

Nancy, , France

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, , France

Institut Curie; Oncologie Medicale

Paris, , France

GH Paris Saint Joseph; Hopital De Jour Oncologie

Paris, , France

HOPITAL TENON; Cancerologie Medicale

Paris, , France

Clinique Francheville; Radiotherapie

Périgueux, , France

Institut Jean Godinot; Oncologie Medicale

Reims, , France

Centre Eugene Marquis; Unite Huguenin

Rennes, , France

Clinique de L'Union; Oncologie

Saint-Jean, , France

Institut de Cancerologie de La Loire; Radiotherapie

Saint-Priest-en-Jarez, , France

Centre Paul Strauss; Oncologie Medicale

Strasbourg, , France

Clinique Pasteur; Oncologie Medicale

Toulouse, , France

Centre Henry S Kaplan - CHU Bretonneau ; service oncologie

Tours, , France

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, , France

Countries

France

References

Coudert B, Pierga JY, Mouret-Reynier MA, Kerrou K, Ferrero JM, Petit T, Kerbrat P, Dupre PF, Bachelot T, Gabelle P, Giard S, Coeffic D, Bougnoux P, Prevost JB, Paintaud G, Thibault G, Hernandez J, Coudert M, Arnould L, Berriolo-Riedinger A. Use of [(18)F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [(18)F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial. Lancet Oncol. 2014 Dec;15(13):1493-1502. doi: 10.1016/S1470-2045(14)70475-9. Epub 2014 Oct 30.

Reference Type: DERIVED

PMID: 25456368 (View on PubMed)

Other Identifiers

2009-013410-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML22229

Identifier Type: -

Identifier Source: org_study_id