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

March 15, 2018 updated by: Hoffmann-La Roche

An Open-Label, Randomized, Multicenter, Phase II, Non Comparative, Exploratory Study on Neoadjuvant Treatment With Trastuzumab Plus Docetaxel Plus Bevacizumab According to Positon Emission Tomography (PET) Value Modification in Patients With Early Stage HER2 Positive Breast Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

152

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Arras, France, 62000
        • Centre Radiotherapie Marie Curie
      • Beauvais, France, 60021
        • Centre Hospitalier; Hematologie-Oncologie
      • Bordeaux, France, 33000
        • Clinique Tivoli; Sce Radiotherapie
      • Brest, France, 29200
        • Hopital Augustin Morvan; Federation De Cancerologie
      • Clermont Ferrand, France, 63011
        • Centre Jean Perrin; Hopital De Jour
      • Clermont Ferrand, France, 63050
        • Pole Sante Republique;Oncologie Hematologie
      • Dijon, France, 21079
        • Centre Georges Francois Leclerc; Oncologie 3
      • Grenoble, France, 38000
        • Institut Daniel Hollard
      • La Roche Sur Yon, France, 85925
        • Centre Hospitalier Départemental Les Oudairies
      • Limoges, France, 87042
        • Hopital Dupuytren; Oncologie Medicale
      • Lyon, France, 69373
        • Centre Leon Berard; Oncologie Genetique
      • Metz, France, 57000
        • Hopital Clinique Claude Bernard; Oncologie Medicale
      • Montlucon, France, 03100
        • Ch De Montlucon; Sce Med Interne Hemato Onco
      • Montpellier, France, 34298
        • Institut régional du Cancer Montpellier
      • Nancy, France, 54100
        • Centre D'Oncologie de Gentilly; Oncology
      • Nice, France, 06189
        • Centre Antoine Lacassagne; Hopital De Jour A2
      • Paris, France, 75231
        • Institut Curie; Oncologie Medicale
      • Paris, France, 75970
        • HOPITAL TENON; Cancerologie Medicale
      • Paris, France, 75674
        • GH Paris Saint Joseph; Hopital De Jour Oncologie
      • Perigueux, France, 24000
        • Clinique Francheville; Radiotherapie
      • Reims CEDEX, France, 51056
        • Institut Jean Godinot; Oncologie Medicale
      • Rennes, France, 35042
        • Centre Eugene Marquis; Unite Huguenin
      • Saint Jean, France, 31240
        • Clinique de L'Union; Oncologie
      • St Priest En Jarez, France, 42271
        • Institut de Cancerologie de La Loire; Radiotherapie
      • Strasbourg, France, 67065
        • Centre Paul Strauss; Oncologie Medicale
      • Toulouse, France, 31076
        • Clinique Pasteur; Oncologie Medicale
      • Tours, France, 37044
        • Centre Henry S Kaplan - CHU Bretonneau ; service oncologie
      • Vandoeuvre Les Nancy, France, 54511
        • Centre Alexis Vautrin; Oncologie Medicale

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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).
Other Names:
  • Avastin
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).
Other Names:
  • Taxotere
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).
Other Names:
  • Herceptin
Procedure: 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).
Radiation: 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.
Drug: 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.
Active Comparator: 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.
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).
Other Names:
  • Taxotere
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).
Other Names:
  • Herceptin
Procedure: 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).
Radiation: 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.
Drug: 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.
Active Comparator: 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.
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).
Other Names:
  • Taxotere
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).
Other Names:
  • Herceptin
Procedure: 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).
Radiation: 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.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants With Pathological Complete Response as per Chevallier's Classification as Reviewed by an Independent Committee
Time Frame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants With Pathological Complete Response According to Chevallier's Classification as per Local Procedures
Time Frame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Percentage of Participants With Pathological Complete Response According to Sataloff's Classification as Reviewed by an Independent Committee
Time Frame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Percentage of Participants With Ultrasound Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Neodajuvant treatment period (21 weeks)
Neodajuvant treatment period (21 weeks)
Percentage of Participants With Conservative Surgery Post Neoadjuvant Treatment
Time Frame: Week 20 (between Day 28 and Day 35 after the Cycle 6, cycle length=21 days)
Week 20 (between Day 28 and Day 35 after the Cycle 6, cycle length=21 days)
Local Relapse-Free Interval (LRFI) According to Modified RECIST Criteria
Time Frame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Disease-Free Survival (DFS) According to Modified RECIST Criteria
Time Frame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Distant Disease-Free Interval (DDFI) According to Modified RECIST Criteria
Time Frame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Overall Survival
Time Frame: Baseline up to occurrence of death (up to 5 years)
Baseline up to occurrence of death (up to 5 years)
Percentage of Participants With Adverse Events
Time Frame: Baseline up to 5 years
Baseline up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2010

Primary Completion (Actual)

December 13, 2017

Study Completion (Actual)

December 13, 2017

Study Registration Dates

First Submitted

June 10, 2010

First Submitted That Met QC Criteria

June 10, 2010

First Posted (Estimate)

June 11, 2010

Study Record Updates

Last Update Posted (Actual)

March 16, 2018

Last Update Submitted That Met QC Criteria

March 15, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML22229
  • 2009-013410-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Senegal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe