Bevacizumab With or Without Cyclophosphamide and Methotrexate: A Pilot Study in Women With Operable Breast Cancer

November 26, 2013 updated by: Harold J. Burstein, MD, PhD

Anti-Angiogenesis Treatment After Preoperative Chemotherapy: A Pilot Study in Women With Operable Breast Cancer

The purpose of this research study is to study the effects (good and bad) of bevacizumab alone, bevacizumab with low-dose continuous chemotherapy (called metronomic chemotherapy), or bevacizumab with capecitabine, on you and your cancer. The goals of the study will be to:

  • Examine the safety of these drugs
  • See how easy or difficult it is to be treated with them
  • Monitor for any signs of recurrent cancer
  • Look at blood markers that might indicate how the treatment is working

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is broken into 4 groups (A, B, C, and D). Enrollment closed to all groups in May 2008.

The first forty subjects (Group A) in this study were treated with Bevacizumab only, which is given through a vein over 1-2 hours every 3 weeks, for a total of approximately 12 months (17 cycles). Each cycle consists of 3 weeks.

The next forty subjects (Group B) were treated with Bevacizumab and metronomic CM chemotherapy. These subjects took cyclophosphamide (1 pill by mouth every day), methotrexate, (1 pill taken by mouth twice a day for the first two days of each week) and Bevacizumab (once every 3 weeks). The treatments with cyclophosphamide, methotrexate and Bevacizumab will continue for approximately 6 months (8 cycles). Then for the next 6 months, they received Bevacizumab treatments only. The total time on this study will be about 12 months (17 cycles).

The next forty subjects (Group C) were treated with Bevacizumab and Capecitabine chemotherapy. These subjects took Capecitabine pills twice a day for 14 days, then one week of rest, to complete a 21-day cycle. There will be a total of 6 cycles of Capecitabine, meaning 18 weeks of treatment with both Capecitabine and Bevacizumab. Then received Bevacizumab treatments only (11 cycles) to complete 12 months of therapy. Total duration of your treatment will be about 12 months or 17 cycles of therapy.

The last forty subjects (Group D) are being treated with Bevacizumab and Capecitabine chemotherapy on a different schedule. These subjects will take Capecitabine pills twice a day for 7 days, then one week of rest and repeat this for a total of 24 weeks (6 cycles). Each cycle will last for 4 weeks (28 days). There will be a total of 6 cycles of Capecitabine, meaning 24 weeks of treatment with both Capecitabine and Bevacizumab. Bevacizumab will be given every two weeks for a total of 24 weeks (6 cycles). Then they will receive Bevacizumab treatments only, every 3 weeks for additional 27 weeks (9 cycles) to complete 12 months of therapy. For the last 9 cycles of Bevacizumab therapy each cycle will consist of 3 weeks. Total duration of treatment will be about 12 months or 15 cycles of therapy.

Study Type

Interventional

Enrollment (Actual)

164

Phase

  • Not Applicable

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

  • United States
    • California
      • San Francisco, California, United States, 94122
        • University of California, San Francisco
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27701
        • University of North Carolina

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

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast cancer, preoperative stages II-III per AJCC 6th edition, based on baseline evaluation by clinical examination and/or breast imaging
  • Patients must have completed preoperative (neoadjuvant) chemotherapy with a standard chemotherapy regimen. No more chemotherapy should be planned.
  • Patients must have completed definitive resection of primary tumor with adequate excision of gross disease.
  • For patients receiving adjuvant radiation therapy, treatment must be completed prior to initiation of protocol therapy.
  • Patients must have the presence of significant residual invasive disease on pathologic review following their preoperative chemotherapy.
  • LVEF > institutional limits of normal after preoperative chemotherapy, as assessed by ECHO or nuclear medicine gated study, within 30 days prior to initiating protocol-based treatment.
  • ECOG performance status 0-1

Exclusion Criteria:

  • Inadequate organ function, as measured by laboratory assessment after preoperative chemotherapy and within 14 days of beginning protocol-based treatment
  • Patients with metastatic disease are ineligible.
  • Known HIV infection
  • Patients may not be pregnant, expect to become pregnant, plan to conceive a child while on study, or breastfeeding
  • Uncontrolled intercurrent illness
  • Non-healing wounds or major surgical procedures (such as breast surgery) other than that for venous access device or diagnostic study are not permitted within 28 day prior to enrollment
  • History of abdominal fistula, GI perforation, intra-abdominal abscess, or serious, non-healing wound, ulcer, or bone fracture within 6 months prior to initiating bevacizumab
  • Patients with any history of arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular event (CVA), unstable angina, or myocardial infarction (MI) within the past 6 months. Patients with clinically significant peripheral arterial disease should also be excluded
  • History of bleeding diathesis or coagulopathy
  • History of grade 3 or 4 allergic reactions to compounds of similar chemical or biologic composition to cyclophosphamide (such as other alkylating agents) or methotrexate (such as other antimetabolites)
  • Prior history of malignancy treated without curative intent, excluding nonmelanomatous skin cancer
  • Patients with large or rapidly accumulating pleural or abdominal effusions
  • Current use of anticoagulants is allowed as long as patients have been on a stable dose for more than two weeks with stable INR
  • Chronic therapy with full dose aspirin (< 325 mg/day) or standard non-steroidal anti-inflammatory agents is allowed
  • Patients may not receive other investigational agents while on study

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
Bevacizumab Alone
Drug: Bevacizumab
Group A: Once every 3 weeks for 12 months Group B: Once every 3 weeks for 12 months
Other Names:
  • Avastin
Experimental: Group B
Bevacizumab with cyclophosphamide and methotrexate
Drug: Bevacizumab
Group A: Once every 3 weeks for 12 months Group B: Once every 3 weeks for 12 months
Other Names:
  • Avastin
Drug: Cyclophosphamide
Once a day for 6 months
Other Names:
  • Cytoxan
Drug: Methotrexate
Twice daily for the first two days of every week for 6 months
Other Names:
  • amethopterin
Experimental: Group C
capecitabine, 14 days on/7 days off scheduling, and bevacizumab
Drug: Bevacizumab
Group A: Once every 3 weeks for 12 months Group B: Once every 3 weeks for 12 months
Other Names:
  • Avastin
Drug: Capecitabine

Capecitabine: 2000 mg/m2 a day, on Days 1-14 of a 21 day cycle, for at total of 6 cycles (18 weeks)

Bevacizumab: 15 mg/kg IV day 1 every 3 weeks x 1 year (17 cycles)

Other Names:
  • Xeloda
Experimental: Group D
capecitabine 7 days on/7 days off scheduling, and bevacizumab
Drug: Bevacizumab
Group A: Once every 3 weeks for 12 months Group B: Once every 3 weeks for 12 months
Other Names:
  • Avastin
Drug: Capecitabine

Capecitabine: 2000 mg/m2 a day, on Days 1-14 of a 21 day cycle, for at total of 6 cycles (18 weeks)

Bevacizumab: 15 mg/kg IV day 1 every 3 weeks x 1 year (17 cycles)

Other Names:
  • Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The Completion Rate of 1 Year of Bevacizumab Therapy for All Four Cohorts
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

Harold J. Burstein, MD, PhD

Collaborators

Beth Israel Deaconess Medical Center
Genentech, Inc.
University of California, San Francisco
Indiana University School of Medicine
University of North Carolina

Investigators

  • Principal Investigator: Harold J Burstein, MD, PhD, Dana-Farber Cancer Institute

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

June 1, 2005

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

July 13, 2005

First Submitted That Met QC Criteria

July 19, 2005

First Posted (Estimate)

July 21, 2005

Study Record Updates

Last Update Posted (Estimate)

December 24, 2013

Last Update Submitted That Met QC Criteria

November 26, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-055

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.

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