Preoperative Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab in Operable Breast Cancer - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Genentech Massachusetts General Hospital Brigham and Women's Hospital
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00546156

Purpose

Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Bevacizumab is an antibody which works differently from the way other chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors by binding to a substance found on cancer cells called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment of breast cancer. Another goal of this research is to determine whether we can develop a way to identify tumors that will respond well to this study treatment.

Condition	Intervention	Phase
Breast Cancer	Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Bevacizumab	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Myocet Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study of Preoperative Dose-Dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel (T) With Bevacizumab in ER+ and/or PR+, HER2-Negative Operable Breast Cancer

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

Primary Outcome Measures:

To determine the pathologic complete response rate after preoperative therapy in this patient population. [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
To test the hypothesis that the luminal B molecular subtype of hormone receptor positive breast cancer is significantly more responsive than the luminal A subtype to preoperative therapy with this treatment regimen. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the relationship between clinical subtype and residual cancer burden. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
To determine the clinical response rate, defined as number of partial and complete responses. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
To determine the feasibility and toxicity of administering bevacizumab in combination with AC followed by T as preoperative therapy. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Evaluate biomarkers in blood and tissue and correlate with pCR and RCB. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
To determine if bevacizumab monotherapy results in a decrease in interstitial fluid pressure. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Standard chemotherapy regimen

One intravenous dose given followed 2 weeks later with standard chemotherapy drugs and bevacizumab given intravenously in 8 two-week cycles.

Detailed Description:

To prepare for the surgery that will occur at the end of the study treatment, a small "clip" will be placed into the tumor area so that the surgeon can locate the site of the tumor at the time of surgery. This is a standard procedure for breast cancer.
During the clip placement, a needle will be inserted into the tumor to measure interstitial fluid pressure (IFP measurement). IFP is done for research purposes to help understand how the tumor responds to the study treatment.
Study treatment will begin with one dose of bevacizumab alone, followed two weeks later by chemotherapy and bevacizumab in eight two-week cycles.

The study treatment will be given intravenously in the clinic.

After the first dose of bevacizumab and prior to starting chemotherapy, a needle biopsy of the breast tumor will be performed for research purposes.

A second measurement of IFP will also be done at this time.

During the treatment period, tests and procedures will be performed at specified intervals and include the following: research MRI, physical exams, blood tests, urine tests, EKG, and MUGA or ECHO.
Surgery to remove the tumor will occur no less than four weeks after the last dose of Paclitaxel.

Eligibility

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

Criteria

Inclusion Criteria:

Documented primary invasive breast cancer by histologic assessment
Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard immunohistochemical methods. Tumors must be negative for HER2.

There must be sufficient sample for further protocol-specified immunohistochemical analysis

Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in protocol
18 year of age or older
Performance status of 0 or 1 by ECOG criteria
Use of an effective means of contraception in subjects of childbearing potential
Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to starting therapy.
Patients taking exogenous sex-steroid hormone treatments for any reason at the time of diagnosis must discontinue all hormonal treatments at least 2 weeks prior to enrollment
Patients must have preoperative treatment within 60 days of initial diagnosis of breast cancer
No other malignancy that requires on-going treatment
Normal organ function as outlined in the protocol

Exclusion Criteria:

Prior cytotoxic chemotherapy or radiation for the current breast cancer
Patients with inflammatory breast cancer
HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be negative by FISH
Known metastatic (Stage IV) disease
Other investigational agents within 4 weeks prior to the start of study treatment
Life expectancy of less than 6 months
Peripheral neuropathy greater than or equal to grade 2
Inadequately controlled hypertension
Any prior history of hypertensive crisis or hypertensive encephalopathy
NYHA grade II or greater congestive heart failure
History of prior myocardial infarction
History of unstable angina within 12 months prior to study enrollment
Any history of stroke or transient ischemic attack at any time
Known CNS disease
Significant vascular disease
Symptomatic peripheral vascular disease
Evidence of significant bleeding within 6 months of study; any serious non-healing wound, skin ulcers, or bone fracture; any abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; any major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during course of study.
Known HIV positive
Unwilling to undergo pretreatment biopsy and consent to acquisition of archival tissue
Pregnant of lactating
Known hypersensitivity to any component of bevacizumab

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00546156

Contacts

Contact: Ian Krop, MD, PhD

617-632-3427

ikrop@partners.org

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Ian Krop, MD, PhD
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Eric P. Winer, MD
Dana-Farber at Faulkner Hospital	Recruiting
Boston, Massachusetts, United States, 02130

Sponsors and Collaborators

Dana-Farber Cancer Institute

Genentech

Massachusetts General Hospital

Brigham and Women's Hospital

Investigators

Principal Investigator:

Ian Krop, MD, PhD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( Ian Krop, MD, PhD )
Study ID Numbers:	07-130
Study First Received:	October 17, 2007
Last Updated:	January 16, 2009
ClinicalTrials.gov Identifier:	NCT00546156 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

ER positive
PR positive

Study placed in the following topic categories:

Skin Diseases
Immunologic Factors
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Bevacizumab
Angiogenesis Inhibitors
Immunosuppressive Agents
Doxorubicin

Anti-Bacterial Agents
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Breast Diseases
Skin Diseases
Growth Substances

Mitosis Modulators
Breast Neoplasms
Antimitotic Agents
Angiogenesis Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Doxorubicin
Neoplasms
Paclitaxel
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009