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
18 Years
N/A
Both
Breast Cancer
Trial Information
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
- 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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population.
Outcome Description:
Pathological Complete response is defined as complete disappearance of invasive tumor in the breast at the time of surgery
Outcome Time Frame:
3 Years
Safety Issue:
No
Principal Investigator
Ian Krop, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Institutional Review Board
Study ID:
07-130
NCT ID:
NCT00546156
Start Date:
October 2007
Completion Date:
December 2012
Related Keywords:
- Breast Cancer
- ER positive
- PR positive
- Breast Neoplasms
Name | Location |
|---|---|
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| New Hampshire Oncology-Hematology PA | Hooksett, New Hampshire 03106 |
| Dana-Farber at Faulkner Hospital | Boston, Massachusetts 02130 |
