Clinical trial NCT00546156: Preoperative Dose-dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab in Operable Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER positive
PR positive
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Massachusetts General Hospital
name: Brigham and Women's Hospital
name: New Hampshire Oncology-Hematology PA
First posted: 2007-10-18
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population.
timeFrame: 3 Years
Secondary outcomes:
measure: Decrease in Interstitial Fluid Pressure.
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber at Faulkner Hospital
state: Massachusetts
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology PA
state: New Hampshire
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Ian Krop, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: