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

Running, not enrolling · Phase 2

Conditions studied: Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Castration-Resistant Prostate Carcinoma, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, HER2-Positive Breast Carcinoma, Locally Advanced Breast Carcinoma, Locally Advanced Gastric Carcinoma, Locally Advanced Malignant Solid Neoplasm, Locally Advanced Ovarian Carcinoma, Locally Advanced Pancreatic Carcinoma, Locally Advanced Prostate Carcinoma, Metastatic Breast Carcinoma, Metastatic Gastric Carcinoma, Metastatic Malignant Solid Neoplasm, Metastatic Ovarian Carcinoma, Metastatic Pancreatic Carcinoma, Metastatic Prostate Carcinoma, Platinum-Sensitive Ovarian Carcinoma, Recurrent Breast Carcinoma, Recurrent Gastric Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Pancreatic Carcinoma, Recurrent Prostate Carcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8

In brief

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.

Key facts

Study ID: NCT04550494
Run by: National Cancer Institute (NCI)
People needed: 29
Starts: 2021-04-26
Expected to finish: 2027-07-14
Last updated by the study team: 2026-07-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam
Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements
The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration
Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed
Ability to understand and the willingness to sign a written informed consent document
Patients must have recurrent, locally advanced or metastatic disease
Patients must have progressed on or after at least one line of standard-of-care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC
PATIENTS WITH OVARIAN CANCER:
All patients with ovarian cancer should have one prior platinum-based therapy
Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible

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

Where it is running

UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States
National Institutes of Health Clinical Center — Bethesda, Maryland, United States
University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States

Full record on ClinicalTrials.gov

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