Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer

Study Overview
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Brief Summary
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This trial provides a unique opportunity in that it combines genomic, proteomic and pharmacogenomic assessments in patients receiving chemotherapy for advanced breast cancer. To date no other trials have analyzed gene and protein expression at the same time points in the same patient, combined with clinical outcome. Similar to previous attempts to predict response based on expression of a single gene or protein, we expect that neither genomic or proteomic profiling alone will be sufficient to optimize therapy. Rather, we expect an iterative process that combines information gleaned from both platforms, modified to avoid toxicity based on pharmacogenomics.

Detailed Description
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OUTLINE: This is a multi-center study. Sample Collection: Core biopsy Blood sample 28-day Cycle Treatment Regimen: Paclitaxel 90 mg/m2 IV D1, 8, and 15 Avastin 10 mg/kg IV D1 and 15 ECOG Performance Status of 0 or 1 Life Expectancy: Not specified Hematopoietic: Platelet count > 100,000/mm³ Absolute neutrophil count > 1200/mm³ PTT < 1.5 x upper limit of normal INR < 1.5 x upper limit of normal Hepatic: Total bilirubin < 1.5 mg/dL SGOT (AST) < 2 x upper limit of normal Renal: Not specified Cardiovascular: Clinically significant cardiovascular or cerebrovascular disease including prior myocardial infarction (within 6 months prior to study entry), unstable angina, Grade II or greater peripheral vascular disease, New York Heart Association (NYHA) Grade II or greater congestive heart failure, hypertensive crises, hypertensive encephalopathy or uncontrolled hypertension (SBP>150, DBP>100).

Official Title
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Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: Core Biopsy
* Procedure: Blood Collection
* Drug: Paclitaxel
* Drug: Avastin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the breast with measurable locally recurrent, locally advanced (that is not amenable to resection with curative intent), or metastatic disease. Patients must consent to have a biopsy performed to obtain fresh tissue or be able to identify a FFPE tissue block in which tissue samples can be obtained to complete the testing for this study. Planned chemotherapy regimen of paclitaxel and Avastin for the treatment of metastatic breast cancer. Females age > 18 years Written informed consent and HIPAA authorization for release of personal health information. Exclusion Criteria: Patients must not have had chemotherapy for locally recurrent or metastatic breast cancer. Hormonal therapy for locally recurrent or metastatic disease must have been discontinued at least 2 weeks prior to study entry. Patients must not have had adjuvant or neoadjuvant taxane therapy within 12 months prior to study entry. Breast cancer overexpressing HER-2 (gene amplification by FISH or 3+ overexpression by immunohistochemistry) are not eligible unless they have received prior therapy with Herceptin. Patients must not have had a major surgical procedure within 4 weeks prior to study entry. (Placement of vascular access device, and breast biopsy, will not be considered major surgery.) Patients must not have had a minor surgical procedure, placement of an access device, or fine needle aspiration within 7 days of starting protocol therapy. Patients must not have had radiation within 2 weeks prior to study entry. Previously radiated area(s) must not be the only site of disease for study entry. Patients must not have a history of bleeding diathesis or have used anticoagulant therapy within 10 days of study entry. (Low dose anticoagulant therapy to maintain patency of a vascular access device is allowed.) Patients with a history of deep vein thrombosis or pulmonary embolism are not eligible. Aspirin usage (> 325 mg/day) or other nonsteroidal anti-inflammatory medications known to inhibit platelet function daily are not allowed within 10 days prior to study entry. Patients currently using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal). Patients must not have a history of TIA or CVA within 6 months prior to study entry. Patients must not have a history or radiologic evidence of CNS metastases including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement (head CT or MRI must be obtained within 6 weeks prior to study entry). Patients must not have a non-healing wound or fracture. Patients must not have a hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies. Females must not be pregnant or breastfeeding. Females of childbearing potential must use an accepted and effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 3 month period thereafter. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry Urine protein: creatinine (UPC) ratio > 1.0 at baseline or urine protein dipstick > 2+.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>Paclitaxel 90 mg/m2 IV D1, 8, and 15 + Avastin 10 mg/kg IV, day 1 and 15 | Procedure: Core Biopsy<br>* biopsy<br>Procedure: Blood Collection<br>* Blood/serum sample<br>Drug: Paclitaxel<br>* Paclitaxel 90 mg/m2 IV, day 1, 8 and 15<br>Drug: Avastin<br>* Avastin 10 mg/kg IV, day 1 and 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate tumor gene expression (genomic profile) with response to paclitaxel + Avastin in patients with advanced breast cancer |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate serum and tumor proteomic profiles with response; To compare serum and tissue proteomic analyses; To compare genomic and proteomic profiles; To correlate toxicity and/or response with drug-specific pharmacogenomic parameters. |  | 36 months |