Talazoparib for the Treatment of BRCA 1/2 Mutant Metastatic Breast Cancer

Active:	Yes
Cancer Type:	Breast Cancer	NCT ID:	NCT03990896
Trial Phases:	Phase II	Protocol IDs:	19-188 (primary) NCI-2019-07732
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Dana-Farber Harvard Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT03990896

Summary

This phase II trial studies how well talazoparib works for the treatment of breast cancer with a BRCA 1 or BRCA 2 gene mutation that has spread to other places in the body (metastatic). Talazoparib is a study drug that inhibits (stops) the normal activity of certain proteins called “poly (ADP-ribose) polymerases” also called “PARPs”. PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as talazoparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. PARPs are needed to repair mistakes that can happen in DNA when cells divide. If the mistakes are not repaired, the defective cell will usually die and be replaced. Cells with mistakes in their DNA that do not die can become tumor cells. Tumor cells may be killed by a study drug, like talazoparib, that stops the normal activity of PARPs. Talazoparib may be effective in the treatment of metastatic breast cancer with BRCA1 or BRCA2 mutations.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate the efficacy of talazoparib, as assessed by progression-free survival in patients with metastatic breast cancer harboring deleterious somatic BRCA 1 or 2 mutations, as detected by circulating cell-free deoxyribonucleic acid (cfDNA) or metastatic tumor tissue biopsy.

SECONDARY OBJECTIVES:
I. To evaluate the objective response rate (ORR) in patients with metastatic breast cancer and deleterious somatic BRCA 1 or 2 mutations treated with talazoparib.
II. To evaluate the safety/tolerability, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading, in patients with metastatic breast cancer harboring deleterious somatic BRCA 1 or 2 mutations, as detected by cfDNA or metastatic tumor tissue biopsy.
III. To prospectively monitor serial changes in BRCA mutant allelic fraction (MAF) by cfDNA in response to treatment with talazoparib, and correlate results with outcomes in patients with metastatic somatic BRCA cfDNA or tumor tissue mutant breast cancer. (exploratory objective)
IV. To assess the impact of pre-existing resistance mutations at baseline, particularly BRCA reversion mutations, based on pre-treatment cfDNA or metastatic tumor tissue analysis, on clinical outcomes with talazoparib, in patients with somatic BRCA mutant metastatic breast cancer. (exploratory objective)
V. To compare paired pre-and post-treatment liquid biopsies (and metastatic tissue biopsy if done prior to trial entry), and to identify potential novel targets for future combination studies. (exploratory objective)
VI. Determine the rate of positivity of the Cancer Risk B (CR-B) assay in patients with somatic BRCA mutations in cell-free DNA or metastatic tumor tissue biopsy who are not known to be germline BRCA1/2 carriers, and correlate CR-B positivity with talazoparib response. (Exploratory objective)

OUTLINE:
Patients receive talazoparib orally (PO) once daily (QD). Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 90 days, then every 3 months up to 2 years.

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