Preoperative Bevacizumab and Trastuzumab With ABI-007 and Carboplatin in HER2+ Breast Cancer

SCRI Development Innovations

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: nab-paclitaxel; Drug: Trastuzumab; Drug: Bevacizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00392392

SCRI BRE 83

Details and patient eligibility

About

This trial combines trastuzumab and bevacizumab monoclonal antibodies, with ABI-007 and carboplatin, as neoadjuvant therapy in previously untreated locally advanced breast cancers demonstrating HER2 gene amplification. It is hoped that this novel combination will result in increased pathologic response rates that will translate into long term outcome improvements in HER2 positive patients with locally advanced breast cancer.

Full description

All eligible patients will receive induction chemotherapy prior to consideration of primary surgical intervention. If surgical intervention is deemed not to be in the best interest of the patient, patient will go off study at the time of evaluation for surgery. Upon completion of chemotherapy and surgery, all ER + and/or PR + patients will be placed on Tamoxifen 20 mg/qd or an aromatase inhibitor.

Induction preoperative therapy:

• Bevacizumab
• Trastuzumab
• ABI-007
• Carboplatin

Postoperative Adjuvant Therapy:

• Bevacizumab
• Trastuzumab

Enrollment: 29 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients with histologically confirmed adenocarcinoma of the breast or inflammatory breast cancer
• Clinical stage T 1-4, N 0-3, M0
• FISH+ HER2 gene amplified breast cancer
• 18 years or older
• Normal cardiac function
• Performance status 0-2
• Cannot have received any prior chemotherapy for this disease or cannot have received chemotherapy for any other cancer in the past 5 years.
• Previous diagnosis of noninvasive breast cancer is OK.
• Must have adequate bone marrow, renal and liver function.
• Pregnant or lactating females not allowed.
• Preexisting peripheral neuropathy must be equal to or less than grade 1
• Must have archived tumor tissue for tissue testing.

Exclusion criteria

You cannot be in this study if you any of the following:

• History of cardiac disease, with New York Heart Association Class II or greater with congestive heart failure
• Any heart attack, stroke or TIAs within the last 6 months or serious arrhythmias needing medication; no bleeding diathesis or coagulopathy.
• No prior investigational drug within the last 30 days
• No prior trastuzumab or bevacizumab therapy

There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Intervention

Experimental group

Description:

Patients received treatment with nab-paclitaxel (100 mg/m2 IV days 1, 8, 15) and carboplatin (AUC 6 IV day 1) every 28 days for 6 cycles. Trastuzumab (4 mg/kg loading dose, followed by 2 mg/kg) and bevacizumab (5 mg/kg IV) were administered weekly for 23 weeks, beginning concurrently with chemotherapy. Patients then underwent either mastectomy or breast conserving surgery and pathologic treatment responses were assessed. After surgery, trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered at 3 week intervals for a total of 52 weeks.

Treatment:

Drug: Trastuzumab

Drug: Bevacizumab

Drug: nab-paclitaxel