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

This study has been completed.
Sponsor:
Collaborators:
Genentech
Beth Israel Deaconess Medical Center
Indiana University School of Medicine
University of California, San Francisco
University of North Carolina
Information provided by (Responsible Party):
Harold J. Burstein, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00121134
First received: July 13, 2005
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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

Condition Intervention
Breast Cancer
Drug: Bevacizumab
Drug: Cyclophosphamide
Drug: Methotrexate
Drug: Capecitabine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-Angiogenesis Treatment After Preoperative Chemotherapy: A Pilot Study in Women With Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • The Completion Rate of 1 Year of Bevacizumab Therapy for All Four Cohorts [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 164
Study Start Date: June 2005
Study Completion Date: May 2011
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Avastin
Drug: Cyclophosphamide
Once a day for 6 months
Other Name: Cytoxan
Drug: Methotrexate
Twice daily for the first two days of every week for 6 months
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: Xeloda

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121134

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94122
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
United States, North Carolina
University of North Carolina
Durham, North Carolina, United States, 27701
Sponsors and Collaborators
Harold J. Burstein, MD, PhD
Genentech
Beth Israel Deaconess Medical Center
Indiana University School of Medicine
University of California, San Francisco
University of North Carolina
Investigators
Principal Investigator: Harold J Burstein, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00121134     History of Changes
Other Study ID Numbers: 05-055
Study First Received: July 13, 2005
Results First Received: August 8, 2013
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Bevacizumab
Metronomic Chemotherapy
Breast Cancer Stages II-III
Invasive breast cancer stages II-III

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Methotrexate
Capecitabine
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014