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

Roche

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Docetaxel; Drug: Bevacizumab; Procedure: Surgery; Drug: Hormonal Therapy; Radiation: Radiotherapy; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01142778

2009-013410-26 (EudraCT Number)

ML22229

Details and patient eligibility

About

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.

Enrollment: 152 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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152 participants in 3 patient groups

Trastuzumab, Docetaxel, and Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Procedure: Surgery

Drug: Hormonal Therapy

Drug: Bevacizumab

Drug: Docetaxel

Radiation: Radiotherapy

Trastuzumab and Docetaxel

Active Comparator group

Description:

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.

Treatment:

Drug: Trastuzumab

Procedure: Surgery

Drug: Hormonal Therapy

Drug: Docetaxel

Radiation: Radiotherapy

Trastuzumab and Docetaxel (Standard Regimen)

Active Comparator group

Description:

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.

Treatment:

Drug: Trastuzumab

Procedure: Surgery

Drug: Hormonal Therapy

Drug: Docetaxel

Radiation: Radiotherapy