Phase 2 Study of Gemzar, Taxol & Avastin Combination as 1st Line Treatment for Metastatic Breast Cancer

Study Overview
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Brief Summary
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Single-institution phase 2 trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.

Detailed Description
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This study will evaluate the time-to-progression (TTP) in patients with metastatic breast cancer, receiving 1st line therapy with bevacizumab in combination with paclitaxel and gemcitabine. Secondary objectives will include response rates and overall survival (OS).

Official Title
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Phase II Open Label Study of Gemcitabine, Paclitaxel and Bevacizumab Combination as First Line Treatment for Metastatic Breast Cancer

Conditions
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Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Paclitaxel
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Previously-untreated metastatic breast cancer. May have had prior chest wall irradiation or palliative radiation to bony sites for control of pain or fracture. These sites of disease, however, will not be considered as sites of measurable disease. Use of bisphosphonates will be permitted. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Granulocyte count ≥ 1500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.0 g/dL. Serum glutamic oxaloacetic transaminase (SGOT) / serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x the institutional upper limit of normal (ULN) if alkaline phosphatase is ≤ ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are ≤ ULN. Total bilirubin within institutional limits of normal. Calculated creatinine clearance ≥ 30 mL/min using the formula: Ccr(mL/min) = [(140-age in years) X (wt in kg) X 0.85 (females)]/(72 x serum creatinine in mg/dL) ≥ 18 years of age. Prior anthracycline treatment in the adjuvant setting or prior chest wall radiation must have left ventricular ejection fraction (LVEF) within the institutional range of normal as assessed by pre-treatment multigated acquisition (MUGA) scan or echocardiogram (ECHO). All patients must give signed written informed consent. May have received adjuvant therapy as long as therapy complete > 12 months from study entry. Females of childbearing potential must have a negative pregnancy test taken ≤ 2 weeks prior to study enrollment, and must consent to the use of effective contraception during the study period and for 6months thereafter. EXCLUSION CRITERIA Receiving hormonal therapy Prior treatment for metastatic disease with cytotoxic agents or inhibitors of epidermal growth factor receptor (EGFR) Her2NEU-positive breast cancers, by either immunohistochemistry (IHC) score 3+ or fluorescence in situ hybridization (FISH) Pregnant or lactating. Patients have had active malignancies other than breast cancer in the past 5 years with the exception of in situ carcinoma of the cervix or nonmelanomatous skin cancer. Active or unresolved infection. Pre-existing peripheral neuropathy > Grade 1. Prior history of severe hypersensitivity reaction to paclitaxel, gemcitabine, bevacizumab or drugs formulated with polysorbate 80. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. Blood pressure of >150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction within 6 months History of stroke within 6 months Clinically-significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy Presence of central nervous system or brain metastases Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 Urine protein:creatinine ratio ≥ 1.0 at screening History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 Serious, non-healing wound, ulcer, or bone fracture Inability to comply with study and/or follow-up procedures

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: Phase II 3-drug regimen<br>Gemcitabine + Paclitaxel + Bevacizumab | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles<br>* Other names: Gemzar;Drug: Paclitaxel<br>* Paclitaxel 80 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles<br>* Other names: Taxol;Drug: Bevacizumab<br>* Bevacizumab 10 mg/kg by IV infusion, days 1 and 15 in 28-day cycles<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-Progression (TTP) | Time-to-Progression (TTP) was assessed as the time from start of treatment to progression, as observed on radiographic scans and assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for progressive disease (ie, a 5-mm absolute increase of the sum of the longest diameters of the target lesions in addition to a 20% increase in the sum of the target lesions) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rates | The best overall response was recorded for each participant from randomization until disease progression/recurrence, using any increase from the smallest measurements recorded since randomization as the indicator of Progressive Disease (PD). Overall response was determined on the basis of response at the target and non-target lesions, and the appearance of new lesions, as follows. Target Nontarget New Lesions Overall Response Complete Complete None Overall Complete Response Complete Incomplete response/ None Overall Partial Response Stable Disease (SD) Partial Not PD None Overall Partial Response SD Not PD None Overall Stable Disease PD Any Yes/No Overall PD Any PD Yes/No Overall PD Any Any Yes Overall PD Overall Response Rate (ORR) was assessed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate. | 24 weeks | 
| Overall Survival (OS), Confirmed | Overall Survival (OS) as determined by confirmed date of death. Participants without documentation as either alive or deceased as of 6 years from the start of treatment were considered lost-to-follow-up. | 6 years | 
| Overall Survival (OS), All Participants | Overall Survival (OS), based on date of death or last known date alive | 6 years |