A Study of Avastin (Bevacizumab) in Patients With Inflammatory or Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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This single arm study will assess the efficacy and safety of sequential neoadjuvant chemotherapy and bevacizumab (Avastin), before surgery and/or radiotherapy, in participants with inflammatory or locally advanced operable breast cancer. Participants will receive 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC), followed by paclitaxel, given concomitantly with bevacizumab. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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Phase II, Open Label, Neoadjuvant Study of Bevacizumab in Patients With Inflammatory or Locally Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: 5-fluorouracil
* Drug: Epidoxorubicin
* Drug: Cyclophosphamide
* Drug: Paclitaxel
* Biological: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female participants, >=18 years of age; stage III, or inflammatory breast cancer; estrogen receptor/progesterone receptor (ER/PgR) positive or negative and human epidermal growth factor receptor 2 (HER-2) negative; normal left ventricular ejection fraction (LVEF). Exclusion Criteria: previous chemotherapy/endocrine therapy; evidence of distant metastatic disease; other primary tumors in last 5 years (except for adequately treated cancer in situ of the cervix, or basal cell skin cancer); chronic daily treatment with >325 milligram per day (mg/day) aspirin, or >75mg/day clopidogrel.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab<br>Participants will receive FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. | Drug: 5-fluorouracil<br>* 600 milligrams per meter squared (mg/m^2) as an intravenous (i.v.) bolus over ≤15 minutes every 3 weeks for 4 cycles.<br>Drug: Epidoxorubicin<br>* 90 mg/m^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.<br>Drug: Cyclophosphamide<br>* 600 mg/m^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel was administered at 80 mg/m^2 i.v. over 1 hour weekly for 12 weeks.<br>Biological: Bevacizumab<br>* Bevacizumab was administered at 10 milligrams per kilogram (mg/kg) i.v. every 2 weeks for 6 cycles.<br>* Other names: Avastin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pathological Complete Response Following Principle Investigator Review | Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. | Up to 7.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions. | Up to 7.5 years | 
| Percentage of Participants With Breast-Conserving Surgery | Rate of breast conversing surgery is defined as percentage of participants who achieved breast conversing surgery out of the ITT population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant treatment. | Up to 7.5 years | 
| Percentage of Participants With Disease-Free Interval | Disease-free interval was defined as the time from enrollment until recurrence of tumor or death from any cause, and was estimated using the Kaplan-Meier method. The percentage of participants without events at Months 12, 24, 36, 48, and 60 is presented. | Months 12, 24, 36, 48, and 60 | 
| Overall Survival | Overall survival was defined as the time from enrollment of participant to death from any cause. | Up to 7.5 years | 
| Percentage of Participants Experiencing Any Adverse Event | An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Up to 7.5 years |