Genetic Testing in Predicting Response to Paclitaxel in Women With Breast Cancer

Georgetown University

Status and phase

Terminated

Phase 2

Conditions

Breast Cancer

Treatments

Procedure: neoadjuvant therapy

Procedure: biopsy

Drug: paclitaxel

Genetic: microarray analysis

Drug: Paclitaxel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00088829

GUMC-00310

P30CA051008 (U.S. NIH Grant/Contract)

CDR0000368453

P50CA058185 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Analyzing genes for changes before and after chemotherapy may help doctors predict a patient's response to treatment and help plan the most effective treatment.

PURPOSE: This clinical trial is studying how well genetic testing works in predicting response to paclitaxel in women who have unresected breast cancer.

Full description

OBJECTIVES:

Primary

Determine the feasibility of accruing women with unresected infiltrating carcinoma of the breast to a clinical trial involving serial breast biopsies and administration of neoadjuvant paclitaxel before formal assessment of axillary lymph node status.
Determine a standard protocol template for gene microarray analysis, in terms of the timing and method of collecting tissue samples, before and after administration of neoadjuvant paclitaxel in these patients.
Determine the safety and efficacy of tissue sampling in these patients.

Secondary

Identify gene(s) or gene clusters that exhibit significant differences between responding and non-responding tumors before treatment with neoadjuvant paclitaxel in these patients.
Identify gene(s) or gene clusters that exhibit changes in gene expression before and after the administration of neoadjuvant paclitaxel in these patients.
Compare significant differences in gene expression between responding and non-responding tumors in patients treated with this drug.
Develop, preliminarily, a statistical model utilizing individual genes and/or gene clusters that can best predict response to paclitaxel in these patients.

OUTLINE: This is a pilot, multicenter study.

Patients undergo core needle breast biopsy within 14 days before starting neoadjuvant paclitaxel treatment. Patients receive neoadjuvant paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo core needle breast biopsy 48 hours after the first administration of paclitaxel, upon completion of course 1, and either upon completion of the last course (in patients with clinical or radiographic evidence of residual disease) or during definitive breast surgery. Biopsy samples are analyzed for gene expression by gene microarray analysis.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

Enrollment

22 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

Histologically confirmed infiltrating carcinoma of the breast
- Unresected disease
- High-risk (> 50% risk of relapse) disease, including any of the following high-risk markers:
  - Estrogen receptor- and progesterone receptor- negative
  - Palpable axillary lymph nodes
  - Grade 3 histology
  - S phase fraction > 10%
  - Ki67 > 30%
Disease that warrants combination therapy with doxorubicin, cyclophosphamide, and paclitaxel
HER2/neu negative or positive
Hormone receptor status:
- Not specified

Menopausal status

Known

Performance status

ECOG 0-2
Absolute neutrophil count > 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1. 5 times normal (except for patients with known Gilbert's disease)
Creatinine ≤ 1.5 times normal

Exclusion: