A Phase II Clinical Trial of Bevacizumab Beginning Concurrently With a Sequential Regimen of Doxorubicin and Cyclophosphamide Followed by Docetaxel and Capecitabine as Neoadjuvant Therapy Followed by Postoperative Bevacizumab Alone for Women With Locally Advanced Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Breast Cancer
- Sponsor
- NSABP Foundation Inc
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Pathologic Complete Response (pCR) in the Breast
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Bevacizumab is an angiogenesis inhibitor which means it works to stop blood vessel formation in tumors. Without new blood vessels, the growth of a tumor is slowed. Chemotherapy drugs kill cancer cells more directly. This study will evaluate:
- How bevacizumab, given with chemotherapy before surgery, and then bevacizumab given alone after surgery, will affect locally advanced breast tumors
- Side effects from adding bevacizumab to chemotherapy
- Whether adding bevacizumab to chemotherapy for breast cancer will affect the heart
- If receiving bevacizumab will have any effect on how patients recover from surgery
- Side effects of the combinations of drugs used in this study
Detailed Description
Initial trials of neoadjuvant chemotherapy administered for locally advanced tumors, including those in breast cancer, demonstrated therapy could induce sufficient tumor regression to allow for the resection of otherwise unresectable tumors. Subsequent demonstration of the equivalence of lumpectomy to mastectomy in patients with operable breast cancer, stimulated interest in the concept of using preoperative chemotherapy to reduce large, but operable, primary tumors to allow for lumpectomy in women who would otherwise require a mastectomy. Given the data from previous studies, it is appropriate to continue development of sequential doxorubicin/cyclophosphamide/docetaxel regimens to improve on clinical and pathologic response rates. FB-4 is a Phase II, single arm study for women with locally advanced human epidermal growth factor receptor 2 (HER2)-negative breast cancer diagnosed by core needle biopsy. The primary aim of the study is to determine the pathologic complete response rate in the breast following neoadjuvant chemotherapy combined with bevacizumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be female.
- •The patient must be greater than/equal to 18 years old
- •The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
- •Patients must have clinical Stage IIIA, IIIB, or IIIC disease (American Joint Committee on Cancer \[AJCC\] staging criteria) with a primary breast tumor that is greater than/equal to 2.0 cm measured by clinical exam, unless the patient has inflammatory breast carcinoma, in which case measurable disease is not required.
- •Patients must have the ability to swallow oral medication.
- •The patient's Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or
- •At the time of study entry, blood counts must meet the following criteria:
- •Absolute neutrophil count (ANC) must be greater than/equal to 1200/mm
- •Platelet count must be greater than/equal to 100,000/mm\^
- •Hemoglobin must be greater than/equal to 10 g/dL.
Exclusion Criteria
- •Tumor determined to be strongly HER2-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
- •Excisional biopsy for this primary tumor.
- •Synchronous bilateral invasive breast cancer.
- •Surgical axillary staging procedure prior to study entry (Exceptions: 1) fine needle aspiration (FNA) of an axillary node is permitted for any patient, and 2) although not recommended, a sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.)
- •History of any of the following cancers:
- •Ipsilateral breast cancer: invasive, ductal carcinoma in situ (DCIS) treated with any therapy other than excision
- •Contralateral breast cancer: invasive within the past 5 years (Patients with history of DCIS or synchronous DCIS are eligible)
- •History of non-breast malignancies within the 5 years prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the previous 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
- •Prior therapy with anthracyclines, taxanes, capecitabine, or bevacizumab for any malignancy.
- •Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to study entry. The only exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before study entry and be re-started, if indicated, following chemotherapy.
Arms & Interventions
Doxorubicin+Cyclophosphamide+Bevacizumab
Intervention: Bevacizumab
Doxorubicin+Cyclophosphamide+Bevacizumab
Intervention: Doxorubicin
Doxorubicin+Cyclophosphamide+Bevacizumab
Intervention: Cyclophosphamide
Doxorubicin+Cyclophosphamide+Bevacizumab
Intervention: Capecitabine
Doxorubicin+Cyclophosphamide+Bevacizumab
Intervention: Docetaxel
Outcomes
Primary Outcomes
Pathologic Complete Response (pCR) in the Breast
Time Frame: Approximately 7 months
Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen
Secondary Outcomes
- Reported Adverse Events(Approximately 14 months)
- pCR in the Breast and Nodes(Approximately 7 months)
- Clinical Response Rate (cRR) of the Sequential Regimen(Approximately 6 months)
- Cardiac Events(Assessments throughout; up to 18 months following study entry)
- Progression-free Survival(2 years)
- Overall Survival(2 years)
- Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma).(Two (2) years)