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