NCT02286687

Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes

Phase II Study of the PARP Inhibitor Talazoparib in Advanced Cancer Patients With Somatic Alterations in BRCA1/2, Mutations/Deletions in Other BRCA Pathway Genes and Germline Mutation in BRCA1/2 (Not Breast or Ovarian Cancer)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, do not respond to treatment, or have spread to other parts of the body, and have alterations in the breast cancer, early onset (BRCA) genes. Talazoparib may cause tumor cells to die by blocking an enzyme that protects the tumor cells from damage.

Detailed description

PRIMARY OBJECTIVES: I. To determine whether the PARP inhibitor talazoparib achieves clinical benefit (complete response \[CR\], partial response \[PR\] or stable disease \[SD\] \> 24 weeks) in metastatic or inoperable locally advanced or locally recurrent cancer patients who have somatic mutations or deletions of BRCA1 or BRCA2, mutations or homozygous deletions in other BRCA pathway genes, and germline mutations in BRCA1 or BRCA 2 with cancers other than breast or ovarian cancer. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of talazoparib in this patient population. (Across-indication) II. To determine baseline molecular markers (deoxyribonucleic acid \[DNA\], ribonucleic acid \[RNA\] and protein) or scores (e.g., microsatellite instability positives, and somatic mutation burden) that may predict clinical benefit. (Within-indication) III. To determine pharmacodynamic (PD) markers in tumor, blood and plasma that may predict outcome. (Within-indication) IV. To determine concordance of BRCA1/2 alterations in archival tissue and pre-treatment biopsies. (Within-indication) V. To determine concordance of genomic alterations in tumor and circulating free DNA. (Within-indication) VI. To evaluate the progression free survival (PFS) in patients. (Within-indication) VII. To evaluate the duration of response (DOR) in patients. (Within-indication) VIII. To evaluate the overall survival (OR) in patients. (Within-indication) OUTLINE: Patients receive talazoparib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for 1 year.

Conditions

• Advanced Malignant Neoplasm
• ATM Gene Mutation
• BRCA1 Gene Mutation
• BRCA2 Gene Mutation
• Metastatic Malignant Neoplasm
• PALB2 Gene Mutation
• Recurrent Malignant Neoplasm
• Refractory Malignant Neoplasm

Interventions

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

Timeline

• Start date: 2014-12-22
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2014-11-10
• Last updated: 2026-01-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study