A Study of Avastin (Bevacizumab) in Combination With Xeloda (Capecitabine) and Docetaxel 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 combination first-line treatment with docetaxel + Xeloda + Avastin in patients with inflammatory or locally advanced breast cancer. Patients will receive 3-weekly cycles of Avastin (15mg/kg i.v. on day 1 of each cycle), docetaxel (75mg/m2 i.v. on day 1 of each cycle, after Avastin) and Xeloda (2000mg/m2 p.o. on days 1-15 of each cycle). Four cycles of chemotherapy are planned, plus an optional additional two cycles; after chemotherapy patients will be assessed for surgery. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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An Open Label Study to Assess the Effect of Neoadjuvant Treatment With Docetaxel + Xeloda + Avastin on Pathological Response Rate in Inflammatory or Locally Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: Docetaxel
* Drug: Xeloda


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients, >=18 years of age; HER2-negative, locally advanced (stage II or III) or inflammatory cancer of the breast; ECOG performance status 0-1. Exclusion Criteria: metastatic disease (stage IV); previous treatment for breast cancer; evidence of CNS metastasis; current or recent (within 10 days of first dose of Avastin) use of aspirin (>325mg/day) NSAIDs or full dose anticoagulants for therapeutic purposes; clinically significant cardiovascular disease.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 15mg/kg iv on day 1 of each 3 week cycle<br>Drug: Docetaxel<br>* 75mg/m2 iv on day 1 of each 3 week cycle<br>Drug: Xeloda<br>* 2000mg/m2 po on days 1-15 of each 3 week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Pathological Complete Response (pCR) | pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected. | At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) | The percentage of participants with a best overall response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | Day 1 of Cycles 1-6 | 
| Progression-Free Survival | Progression-free survival was defined as the time from the date of informed consent until the date disease progression was identified, or the date of death from disease progression, whichever occurred first. | Cycles 1-6 | 
| Overall Survival | Overall survival was defined as the time from the date of informed consent until the date of death due to any cause. | Cycles 1-6 | 
| Percentage of Participants Undergoing Breast-Conserving Surgery | The percentage of participants who were able to undergo breast-conserving surgical procedures (segmentectomy plus lymphadenectomy or quadrantectomy plus lymphadenectomy) rather than non-breast conserving procedures (radical mastectomy or modified-radical mastectomy) following 4 or more treatment cycles. | Following Cycle 6 |