This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially effective in patients with BRCA mutations. It is not yet known whether adding talazoparib before standard treatment is safe in treating patients with BRCA mutated breast cancer.
PRIMARY OBJECTIVES: I. To evaluate the feasibility of using talazoparib prior to initiating standard neoadjuvant therapies. II. To evaluate the toxicity profile in women taking talazoparib in the neoadjuvant setting. SECONDARY OBJECTIVES: I. To provide first estimate of clinical response to talazoparib in the neoadjuvant setting in a pilot trial setting. II. To evaluate biomarkers of therapy efficacy as well as initiate patient derived xenograft (PDX) models: targeted or whole exome sequencing for BRCA pathway mutations and other somatic and germline alterations; ribonucleic acid (RNA) sequencing; evaluation of changes in immune response; transcriptional profile to assess triple negative breast cancer (TNBC) subtype, BRCA-ness signature and putative PARP sensitivity predictors; functional proteomics with reverse phase protein array (RPPA); generate PDX models and mammosphere cultures from patient derived tumors; PTEN, gamma-H2A histone family, member x (gamma-H2A.X), Ki-67 and cleaved caspase 3 by immunohistochemistry (IHC). OUTLINE: Patients receive talazoparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice. After completion of study treatment, patients are followed up until the day after definitive breast surgery.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Correlative studies
Given PO
M D Anderson Cancer Center
Houston, Texas, United States
Number of Participants With Overall Pathological Complete Response (pCR)
Pathologic response was documented using the Residual Cancer Burden (RCB) Calculator. Residual cancer burden by ICR will be reported as a categorical variable with four classes (categories) RCB 0 (pCR) which correlates to no invasive disease in breast and lymph, I (minimal RCB), II (moderate RCB), and III (extensive RCB). Up to two fine needle aspirates (FNAs) will also be obtained at each time point for a total of up to 6 FNA's for the trial, which will be used for the patient derived xenograft models. Pre-study biopsies, as well as biopsies within 7 days prior to the completion of 2 months of talazoparib will be collected via diagnostic imaging. During the expansion phase of this trial, ultrasounds will be obtained every 2 cycles (+/- 1 week). Therapy will be discontinued if the Physician or PI indicates clinically significant progression of disease.
Time frame: Up to 6 months
Number of Participants With Grade 4 Toxicities
To assess the toxicity profile of women taking single agent Talazoparib prior to surgery. If greater than 33% of the patients enrolled have either a grade 4 toxicity possibly, probably, or definitely related to the treatment as attributed by the Principal Investigator, or requires a delay in treatment for greater than 4 weeks due to toxicity.
Time frame: up to 6 months
Median Clinical Response to Single Agent Talazoparib
Imaging was the primary measures response with tumor volume shrinkage after 2 months of Talazoparib prior to proceeding with standard chemotherapy for all participants. The clinical response to Talazoparib in the neoadjuvant setting in a pilot trial setting.
Time frame: 2 months
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