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

Phase II Study of Preoperative Bevacizumab and Trastuzumab Administered With ABI-007 and Carboplatin in HER2 Overexpressing Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Trastuzumab; Drug: nab-paclitaxel

Detailed 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

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Nashville, Tennessee, United States, 37023
      • Tennessee Oncology, PLLC

Participation Criteria

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; 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.

Drug: Bevacizumab; Bevacizumab; Other Names: Avastin; Drug: Trastuzumab; Trastuzumab; Other Names: Herceptin; Drug: nab-paclitaxel; ABI-007; Other Names: ABI-007; Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate (PCRR), the Percentage of Patients Who Have No Evidence of Cancer in the Breast or Lymph Nodes Following Surgery	Pathologic complete response was defined as the absence of residual invasive cancer in the breast (pT0) and axillary lymph nodes (pN0).	18 months

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Genentech, Inc.; Celgene Corporation
• Investigators: Principal Investigator: Denise Yardley, MD, SCRI Development Innovations, LLC

Publications and helpful links

General Publications

• Yardley DA, Raefsky E, Castillo R, Lahiry A, Locicero R, Thompson D, Shastry M, Burris HA 3rd, Hainsworth JD. Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+ breast cancer. Clin Breast Cancer. 2011 Oct;11(5):297-305. doi: 10.1016/j.clbc.2011.04.002. Epub 2011 May 5.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 25, 2006
• First Submitted That Met QC Criteria: October 25, 2006
• First Posted (Estimate): October 26, 2006

Study Record Updates

• Last Update Posted (Estimate): September 20, 2013
• Last Update Submitted That Met QC Criteria: September 17, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Trastuzumab; Bevacizumab
• Other Study ID Numbers: SCRI BRE 83