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About
This phase II trial studies if talazoparib works in patients with cancer that has spread to other places in 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.
Full description
PRIMARY OBJECTIVE:
I. Determine the pharmacodynamic (PD) effect of talazoparib in tumor biopsies for patients with aberrations in deoxyribonucleic acid (DNA) damage response genes who have or have not received prior PARP inhibitor treatment (separately).
SECONDARY OBJECTIVE:
I. Determine the response rate (complete response [CR] + partial response [PR]) of treatment with talazoparib in patients with aberrations in DNA damage response genes.
EXPLORATORY OBJECTIVE:
I. Investigate tumor genomic alterations potentially associated with sensitivity or acquired resistance to talazoparib.
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. Patients undergo biopsy and blood sample collection throughout the study. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Enrollment
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Inclusion criteria
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
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 computed tomography (CT) scan, magnetic resonance imaging (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
Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
PATIENTS WITH PANCREATIC CANCER:
All patients with pancreatic cancer should have received prior platinum-containing therapy
PATIENTS WITH BREAST CANCER:
Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy
Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
PATIENTS WITH GASTRIC CANCER:
Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting
PATIENTS WITH PROSTATE CANCER:
Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented
All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy
Patients with castration resistant prostate cancer must have castrate levels of testosterone (< 50 ng/dL [1.74 nmol/L])
Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-AR therapy
Exclusion criteria
Primary purpose
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36 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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