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Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

ConditionsAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Castration-Resistant Prostate CarcinomaClinical Stage III Gastric Cancer AJCC v8Clinical Stage IV Gastric Cancer AJCC v8HER2-Positive Breast CarcinomaLocally Advanced Breast CarcinomaLocally Advanced Gastric CarcinomaLocally Advanced Malignant Solid NeoplasmLocally Advanced Ovarian CarcinomaLocally Advanced Pancreatic CarcinomaLocally Advanced Prostate CarcinomaMetastatic Breast CarcinomaMetastatic Gastric CarcinomaMetastatic Malignant Solid NeoplasmMetastatic Ovarian CarcinomaMetastatic Pancreatic CarcinomaMetastatic Prostate CarcinomaPlatinum-Sensitive Ovarian CarcinomaRecurrent Breast CarcinomaRecurrent Gastric CarcinomaRecurrent Ovarian CarcinomaRecurrent Pancreatic CarcinomaRecurrent Prostate CarcinomaStage II Pancreatic Cancer AJCC v8Stage III Ovarian Cancer AJCC v8Stage III Pancreatic Cancer AJCC v8Stage III Prostate Cancer AJCC v8Stage IV Ovarian Cancer AJCC v8Stage IV Pancreatic Cancer AJCC v8Stage IV Prostate Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors "one after the other" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization Laboratory (MoCha) will be acceptable for determination of eligibility

Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and/or clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled

Deleterious BRCA1 or BRCA2 mutations

Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN

Disqualifiers

Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be >= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be >= 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events

Patients who have had prior treatment with talazoparib are ineligible

Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1/PD-L1 and anti-HER2), which must be completed >= 4 weeks prior to enrollment

Patients who are receiving any other investigational agents

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Talazoparib

    Drug

    Given PO

Treatment groups

36 Participants
are divided into 1 treatment group
Group A: Treatment (talazoparib)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Percent of patients who demonstrate simultaneous Rad51 activation

Will be measured as the percent of patients who demonstrate simultaneous Rad51 activation, defined to be at least 5% cells with at least 5 Rad51 foci, and lack of gamma-H2AX activation, defined to be less than 4% nuclear area positive (NAP), at the cycle 2 day 1 biopsy.

Time frame
At cycle 2 day 1

Secondary outcomes

1

Overall response rate

Will estimate the overall response rate (complete response + partial response) among eligible patients who have received at least one dose of talazoparib. A 95% confidence interval for this response rate will also be computed. For this analysis, response classifications will follow Response Evaluation Criteria in Solid Tumors version 1.1 guidelines.

Time frame
Up to 30 days after last dose

Other outcomes

1

Tumor genomic alterations potentially associated with sensitivity or acquired resistance to talazoparib

Exploratory evaluations will be performed, with results reported with appropriate caveats about the exploratory nature of the analysis, and without formal adjustment for multiple comparisons.

Time frame
Up to 30 days after last dose

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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