Abraxane, Avastin, and Gemcitabine as First-Line Therapy for Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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The investigators hypothesize that the combination of Gemzar®, Abraxane® and Avastin will increase the progression-free survival (PFS) in patients with first line metastatic breast cancer and in patients who received neoadjuvant and/or adjuvant chemotherapy present with definable metastatic disease, 6 or more months after primary treatment.

Detailed Description
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This is a phase 2, single arm study. Participants will be treated with combination Gemzar, Abraxane and Avastin therapy until disease progression. Each treatment cycle is 28 days.

Official Title
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A Phase II Study of Abraxane, Avastin and Gemcitabine for First Line Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Avastin
* Drug: Gemcitabine
* Drug: Abraxane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must either be: treatment-naïve with newly diagnosed her2neu non-overexpressing (non amplified) metastatic (Stage IV) breast cancer, or HER2/neu-negative patients with metastasis diagnosed 6 or more months after completing primary systemic treatment (neoadjuvant, adjuvant chemotherapy). No previous chemotherapy regimen for metastatic breast cancer. 18 years of age or older. Measurable disease as defined by RECIST criteria or evaluable disease. Eastern Cooperative Oncology Group (ECOG) 0-1. Life expectancy greater than 3 months. For female (or male) patients, either pre- or post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control for the duration of the study Provide written informed consent before any study-related procedure not part of normal medical care is conducted Willing and able to comply with the protocol requirement Laboratory parameters as follows: Neutrophils: 1.5 x109/L or greater Platelets: 100 x109/L or greater Hemoglobin: ≥ 9.0 g/dL Serum Creatinine: ≤ 1.5mg/dL Bilirubin: ≤ ULN, except when caused by metastatic disease Alanine transaminase (ALT)/Aspartate transaminase (AST): ≤ 2.5 times the upper limit of the normal range (ULN) except when caused by metastatic disease Urine protein creatinine (UPC) ratio < 1.0 at screening. Exclusion Criteria Previous treatment with gemcitabine. History of Gastrointestinal Bleeding in the previous 3 months. Chemotherapy within 4 weeks prior to enrollment. Radiation therapy or evidence of acute effects of radiation therapy within 2 weeks prior to enrollment. Any major surgery within 4 weeks prior to enrollment. Presence of central nervous system or brain metastases. Urine protein: creatinine ratio ≥ 1.0 at screening. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications). A prior history of hypertensive crisis or hypertensive encephalopathy. Peripheral neuropathy > grade I. Clinical AIDS or known positive HIV serology No concurrent clinically evident malignancy is allowed except inactive non-melanoma skin cancer and inactive cervical cancer diagnosed or other cancer for which the patient has been disease-free for five years. 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 Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to enrollment. Pregnant (positive pregnancy test) or lactating. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment Serious, non-healing wound, ulcer, or bone fracture Inability to comply with study and/or follow-up procedures Participants with serious medical or psychiatric illness that would render chemotherapy unsafe are ineligible. Participants cannot have been in another experimental drug study other than a Bevacizumab cancer study within 4 weeks of the first infusion of these study medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

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: Abraxane, Avastin and Gemcitabine<br>Each treatment cycle is 28 days. Participants will be treated until disease progression: Gemcitabine: 1500 mg/m2 body surface area (BSA) intravenously (IV) over 30 minutes (+/- 5 minutes) on days 1 and 15 of each cycle, followed by; Abraxane: 150 mg/m2 IV over 30 minutes (+/- 5 minutes) on days 1 and 15 of each cycle, followed by; Avastin: 10 mg/kg IV on days 1 and 15 of each cycle. | Drug: Avastin<br> <br> * Other names: Bevacizumab;Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Abraxane<br> <br> * Other names: Albumin-Bound Paclitaxel Formulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-Free Survival | Progression-free survival will be measured from the first dose date to the earliest date of documented evidence of progressive disease or the date of death due to any causes, whichever occurs first. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Partial Response (PR), Complete Response (CR) and Overall Response (ORR) in Study Participants | Rates of partial response (PR), complete response (CR) and overall response (PR+CR = ORR) in study participants according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. | After two cycles, about 60 days | 
| Rate of Toxicity in Study Participants | Determination of safety and side effect profile of the protocol therapy including the rate of toxicity in study participants. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting. | Over the course of study treatment. | 
| Relationship Between Circulating Tumor Cells (CTC) and Disease Progression as Measured by Presence of CTC at Baseline and Over the Course of Study Treatment | Exploration of the relationship between circulating tumor cells (CTC) and disease progression, by measuring CTC at baseline and over the course of treatment. | Baseline, over the course of Treatment, about 1 year | 
| Relationship Between SPARC Expression and Response to Protocol Therapy. | Relationship between SPARC expression and response to this chemotherapy combination and relation to progression free survival. | Baseline, over the course of treatment, about 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer