NCT02282345

Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer

A Pilot Study of Talazoparib as a Neoadjuvant Study in Patients With a Diagnosis of Invasive Breast Cancer and a Deleterious BRCA Mutation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Breast Adenocarcinoma
• Deleterious BRCA1 Gene Mutation
• Deleterious BRCA2 Gene Mutation
• HER2/Neu Negative
• Invasive Breast Carcinoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Talazoparib	Given PO

Timeline

• Start date: 2015-04-16
• Primary completion: 2018-04-26
• Completion: 2022-06-07
• First posted: 2014-11-04
• Last updated: 2022-07-06
• Results posted: 2022-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study