Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response
4 other identifiers
interventional
36
1 country
4
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2021
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 15, 2020
CompletedFirst Posted
Study publicly available on registry
September 16, 2020
CompletedStudy Start
First participant enrolled
April 26, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
May 13, 2026
December 1, 2025
5.6 years
September 15, 2020
May 12, 2026
Conditions
Outcome Measures
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.
At cycle 2 day 1
Secondary Outcomes (1)
Overall response rate
Up to 30 days after last dose
Other Outcomes (1)
Tumor genomic alterations potentially associated with sensitivity or acquired resistance to talazoparib
Up to 30 days after last dose
Study Arms (1)
Treatment (talazoparib)
EXPERIMENTALPatients receive talazoparib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and blood sample collection as well as CT scan or MRI throughout the study.
Interventions
Undergo biopsy
Undergo blood sample collection
Undergo MRI
Undergo CT scan
Eligibility Criteria
You may qualify if:
- 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
- A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L
- Age \>= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Life expectancy of greater than 3 months
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 10 g/dL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (=\< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal
- Creatinine =\< 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl) \>= 60 mL/min/1.73m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73m\^2
- +23 more criteria
You may not qualify if:
- 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
- Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for \>= 1 month without requiring steroid and anti-seizure medication are eligible to participate
- Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (=\< 1 mg/day) is permitted
- Women who are currently lactating
- History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
A P Chen
National Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 15, 2020
First Posted
September 16, 2020
Study Start
April 26, 2021
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
May 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.