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

NCT00121134 | Completed Results DMC

• 1 other identifier: 05-055
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Breast Cancer

Keywords

Bevacizumab; Metronomic Chemotherapy; Breast Cancer Stages II-III; Invasive breast cancer stages II-III

Outcome Measures

Primary Outcomes (1)

• The Completion Rate of 1 Year of Bevacizumab Therapy for All Four Cohorts

  1 year

Study Arms (4)

Group A

EXPERIMENTAL

Bevacizumab Alone

Drug: Bevacizumab

Group B

EXPERIMENTAL

Bevacizumab with cyclophosphamide and methotrexate

Drug: Bevacizumab; Drug: Cyclophosphamide; Drug: Methotrexate

Group C

EXPERIMENTAL

capecitabine, 14 days on/7 days off scheduling, and bevacizumab

Drug: Bevacizumab; Drug: Capecitabine

Group D

EXPERIMENTAL

capecitabine 7 days on/7 days off scheduling, and bevacizumab

Drug: Bevacizumab; Drug: Capecitabine

Interventions

Bevacizumab DRUG

Group A: Once every 3 weeks for 12 months Group B: Once every 3 weeks for 12 months

Also known as: Avastin

Group A; Group B; Group C; Group D

Cyclophosphamide DRUG

Once a day for 6 months

Also known as: Cytoxan

Group B

Methotrexate DRUG

Twice daily for the first two days of every week for 6 months

Also known as: amethopterin

Group B

Capecitabine DRUG

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)

Also known as: Xeloda

Group C; Group D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Harold J. Burstein, MD, PhD: lead
• Genentech, Inc.: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Indiana University School of Medicine: collaborator
• University of California, San Francisco: collaborator
• University of North Carolina: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94122, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of North Carolina

Durham, North Carolina, 27701, United States

Location

Related Publications (1)

• Trapani D, Jin Q, Miller KD, Rugo HS, Reeder-Hayes KE, Traina T, Abdou Y, Falkson C, Abramson V, Ligibel J, Chen W, Come S, Nohria A, Ryabin N, Tayob N, Tolaney SM, Burstein HJ, Mayer EL. Optimizing Postneoadjuvant Treatment of Residual Breast Cancer With Adjuvant Bevacizumab Alone, With Metronomic or Standard-Dose Chemotherapy: A Combined Analysis of DFCI 05-055 and DFCI 09-134/TBCRC 012/ABCDE Clinical Trials. Clin Breast Cancer. 2025 Jun;25(4):e419-e430.e5. doi: 10.1016/j.clbc.2024.12.018. Epub 2024 Dec 31.

  PMID: 39890560 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Cyclophosphamide; Methotrexate; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr Harold J. Burstein
• Organization: DFCI

hal_burstein@dfci.harvard.edu

617-632-3800

Study Officials

• Harold J Burstein, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 13, 2005
• First Posted: July 21, 2005
• Study Start: June 1, 2005
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2011
• Last Updated: December 24, 2013
• Results First Posted: October 14, 2013

Record last verified: 2013-11

Locations

US (5)