Trial Information

Phase II Trial of Neoadjuvant Chemotherapy With Carboplatin and NAB-Paclitaxel in Patients With Locally Advanced and Inflammatory Triple Negative Breast Cancer

PRIMARY OBJECTIVES:

I. To test the hypothesis that carboplatin + nab-paclitaxel (paclitaxel albumin-stabilized
nanoparticle formulation) therapy will demonstrate a promising neoadjuvant pathologic
complete response (pCR) rate for eligible patients.

II. To test the hypothesis that carboplatin + nab-paclitaxel therapy will demonstrate a
promising Symmans 0-1 pathological response rate for eligible patients.

SECONDARY OBJECTIVES:

I To evaluate the overall survival and event-free survival of eligible patients treated with
carboplatin + nab-paclitaxel neoadjuvant chemotherapy.

II. To evaluate the toxicities and tolerance of carboplatin + nab-paclitaxel therapy in this
patient population.

III. To evaluate the role of laboratory correlates in response, toxicity and survival
endpoints.

IV. To procure tissue and perform analysis of gene and protein expression profiles of
pre-treatment primary tumor (estimated success rate: 80%) and residual tumors (25%) and
lymph nodes including the study of tumor niche (50%), studying sequential assessment of
cellular characteristics and gene and protein expression profiles.

V. To identify specific mutations in tumor deoxyribonucleic acid (DNA) in comparison to
adjacent tissue and germ line DNA procured prior to, during, and subsequent to neoadjuvant
chemotherapy, and to detect/measure, as feasible, the presence of such mutations in
fragmented circulating DNA from plasma, and to correlate these mutations with the
presence/characteristics of circulating tumor cells in order to identify prognostic and
predictive indicators of persisting/relapsed disease and targets for therapy.

VI. To assess ribonucleic acid (RNA) (using Mammaprint/Blueprint and 44,000 Agilent platform
gene array), (micro) miRNA and protein profiles in tumor, adjacent tissue and plasma prior
to, during, and at completion of neoadjuvant chemotherapy in order to establish prognostic
and predictive indicators of outcome, markers of persistent/relapsed disease, and targets
for therapy.

VII. To analyze tumor DNA and genomic DNA from plasma by microarray and reverse
transcriptase (RT)-polymerase chain reaction (PCR) analysis to assess copy numbers/single
nucleotide polymorphisms (SNP)/genomic polymorphisms in genes for the purposes of
establishing prognostic and predictive indicators of outcomes; markers of
persistence/relapse disease, drug resistance, and drug metabolism; and targets of therapy.

VIII. To assess the prognostic and predictive value of conventional pathological features
(stage, estrogen and progesterone receptor and human epidermal growth factor receptor
[HER-2] status, presence of lymphovascular invasion, high grade tumor status) in comparison
to such values derived from the molecular approaches.

IX. To procure tumor from the primary and definitive surgical specimen for the purpose of
establishing breast cancer stem cell lines.

X. To procure blood samples for the purpose of identifying and characterizing circulating
tumor cells.

OUTLINE:

Patients receive carboplatin intravenously (IV) over 30 minutes on day 1 and paclitaxel
albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly. Treatment
repeats every 28 days for 4 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 3 months for 4 years and
then every 6 months for 1 year.