Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer
Inflammatory Breast Cancer
Stage IIA Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Triple-negative Breast Cancer
Stage IIB Breast Cancer
Estrogen Receptor Negative
Progesterone Receptor Negative
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Neoadjuvant Chemotherapy With Carboplatin and NAB-Paclitaxel in Patients With Locally Advanced and Inflammatory Triple Negative Breast Cancer|
- pCR or Symmans 0-1 pathological response [ Time Frame: At completion of definitive surgery ] [ Designated as safety issue: No ]A two stage design using MD Anderson criteria of lack of evidence of any residual invasive tumor in breast and/or regional lymph node.
- Overall survival [ Time Frame: 5 years from completion of study treatment ] [ Designated as safety issue: No ]Estimated by the Kaplan-Meier method. The corresponding median survival times (with 90% confidence limits) will be determined.
- Progression-free survival [ Time Frame: 5 years from completion of study treatment ] [ Designated as safety issue: No ]Estimated by the Kaplan-Meier method. The corresponding median survival times (with 90% confidence limits) will be determined.
- Number of patients experiencing serious adverse events (SAEs) graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]SAEs will be characterized by type of adverse event and grade, and by the time of onset in relation to the first day of therapy for each cycle. Attribution of SAEs to treatment (unrelated, unlikely, possible, probable, or definite) will also be reported. The cumulative percentage of patients experiencing treatment-related SAEs and its relationship to treatment duration will also be reported.
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (carboplatin and nab-paclitaxel)
Patients receive carboplatin 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.
Other Names:Drug: paclitaxel albumin-stabilized nanoparticle formulation
Other Names:Other: laboratory biomarker analysis
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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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01525966
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: George Somlo, MD 800-826-4673 email@example.com|
|Principal Investigator: George Somlo, MD|
|City of Hope- South Pasadena Cancer Center||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 firstname.lastname@example.org|
|Principal Investigator: Stephen C. Koehler, MD|
|Principal Investigator:||George Somlo||City of Hope Medical Center|