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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Bevacizumab; Drug: Docetaxel; Drug: Trastuzumab; Procedure: Surgery; Radiation: Radiotherapy; Drug: Hormonal Therapy

• Registration Number: NCT01142778
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-19
• Study First Submitted: 2010-06-10
• Study First Submitted QC: 2010-06-10
• Study First Posted: 2010-06-11
• Primary Completion: 2017-12-13
• Study Completion: 2017-12-13
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-15
• Last Update Posted: 2018-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 152

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trastuzumab, Docetaxel, and Bevacizumab	Surgery	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.
Trastuzumab, Docetaxel, and Bevacizumab	Radiotherapy	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.
Trastuzumab, Docetaxel, and Bevacizumab	Hormonal Therapy	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.
Trastuzumab and Docetaxel	Hormonal Therapy	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.
Trastuzumab and Docetaxel	Surgery	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.
Trastuzumab and Docetaxel	Radiotherapy	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.
Trastuzumab and Docetaxel (Standard Regimen)	Surgery	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.
Trastuzumab and Docetaxel (Standard Regimen)	Radiotherapy	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.
Trastuzumab and Docetaxel (Standard Regimen)	Hormonal Therapy	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.
Trastuzumab, Docetaxel, and Bevacizumab	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.
Trastuzumab, Docetaxel, and Bevacizumab	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 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.
Trastuzumab, Docetaxel, and Bevacizumab	Trastuzumab	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.
Trastuzumab and Docetaxel	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.
Trastuzumab and Docetaxel	Trastuzumab	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.
Trastuzumab and Docetaxel (Standard Regimen)	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.
Trastuzumab and Docetaxel (Standard Regimen)	Trastuzumab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Pathological Complete Response According to Chevallier's Classification as per Local Procedures	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	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)	Neodajuvant treatment period (21 weeks)
Percentage of Participants With Conservative Surgery Post Neoadjuvant Treatment	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	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	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	From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Overall Survival	Baseline up to occurrence of death (up to 5 years)
Percentage of Participants With Adverse Events	Baseline up to 5 years

Trial Locations

Locations (28)

Centre Leon Berard; Oncologie Genetique; 🇫🇷 Lyon, France

Centre D'Oncologie de Gentilly; Oncology; 🇫🇷 Nancy, France

Centre Radiotherapie Marie Curie; 🇫🇷 Arras, France

Centre Hospitalier Departemental Les Oudairies; 🇫🇷 La Roche Sur Yon, France

Hopital Clinique Claude Bernard; Oncologie Medicale; 🇫🇷 Metz, France

Institut régional du Cancer Montpellier; 🇫🇷 Montpellier, France

Centre Antoine Lacassagne; Hopital De Jour A2; 🇫🇷 Nice, France

Institut Daniel Hollard; 🇫🇷 Grenoble, France

Centre Jean Perrin; Hopital De Jour; 🇫🇷 Clermont Ferrand, France

Centre Georges Francois Leclerc; Oncologie 3; 🇫🇷 Dijon, France

Ch De Montlucon; Sce Med Interne Hemato Onco; 🇫🇷 Montlucon, France

Institut Curie; Oncologie Medicale; 🇫🇷 Paris, France

Clinique de L'Union; Oncologie; 🇫🇷 Saint Jean, France

Institut Jean Godinot; Oncologie Medicale; 🇫🇷 Reims CEDEX, France

Centre Henry S Kaplan - CHU Bretonneau ; service oncologie; 🇫🇷 Tours, France

Centre Alexis Vautrin; Oncologie Medicale; 🇫🇷 Vandoeuvre Les Nancy, France

Clinique Tivoli; Sce Radiotherapie; 🇫🇷 Bordeaux, France

Centre Hospitalier; Hematologie-Oncologie; 🇫🇷 Beauvais, France

Hopital Dupuytren; Oncologie Medicale; 🇫🇷 Limoges, France

HOPITAL TENON; Cancerologie Medicale; 🇫🇷 Paris, France

Clinique Francheville; Radiotherapie; 🇫🇷 Perigueux, France

Institut de Cancerologie de La Loire; Radiotherapie; 🇫🇷 St Priest En Jarez, France

Centre Paul Strauss; Oncologie Medicale; 🇫🇷 Strasbourg, France

Hopital Augustin Morvan; Federation De Cancerologie; 🇫🇷 Brest, France

GH Paris Saint Joseph; Hopital De Jour Oncologie; 🇫🇷 Paris, France

Pole Sante Republique;Oncologie Hematologie; 🇫🇷 Clermont Ferrand, France

Clinique Pasteur; Oncologie Medicale; 🇫🇷 Toulouse, France

Centre Eugene Marquis; Unite Huguenin; 🇫🇷 Rennes, France