Clinical trial NCT00537173: Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer
Official title: Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Breast Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Indiana University School of Medicine
name: University of Colorado, Denver
name: Baylor University
name: McGill University
First posted: 2007-09-28
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study population is limited to patients with advanced breast cancer who are receiving paclitaxel + Avastin

Brief summary: 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: 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).

Eligibility criteria: 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+.

Primary outcomes:
measure: To correlate tumor gene expression (genomic profile) with response to paclitaxel + Avastin in patients with advanced breast cancer
timeFrame: 36 months
Secondary outcomes:
measure: 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.
timeFrame: 36 months
Other outcomes:
Locations:
city: Bloomington
country: United States
facility: Cancer Care Center of Southern Indiana
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Houston
country: United States
facility: Baylor College of Medicine - Methodist Breast Center
state: Texas
Study officials:
affiliation: Hoosier Oncology Group, Inc.
name: George Sledge, M.D.
role: PRINCIPAL_INVESTIGATOR
References: