Open-Label Extension and Safety Study of Talazoparib

Study Overview
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Brief Summary
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This is a single-arm, open-label, extended treatment, safety study in patients treated with talazoparib in qualifying studies.

Official Title
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A SINGLE-ARM, OPEN-LABEL, MULTICENTER, EXTENDED TREATMENT, SAFETY STUDY IN PATIENTS TREATED WITH TALAZOPARIB

Conditions
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Cancer

Intervention / Treatment
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* Drug: Talazoparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Female patients of childbearing potential must have a negative pregnancy test before the first dose of talazoparib and must agree to use a highly effective birth control method from the time of the first dose of talazoparib through 45 days after the last dose. Male patients must use a condom when having sex with a pregnant woman or with a woman of childbearing potential from the time of the first dose of talazoparib through 105 days after the last dose. Contraception should be considered for a nonpregnant female partner of childbearing potential. Female patients may not be breastfeeding at the first dose of talazoparib and must not breastfeed during study participation through 45 days after the last dose of talazoparib. Exclusion Criteria: Permanently discontinued from any Medivation sponsored study with talazoparib alone or in combination with another agent. Received an antineoplastic therapy or investigational agent after treatment with talazoparib in the originating protocol. Has a clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, infectious, metabolic, neurologic, psychologic, or pulmonary disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator. Diagnosis of myelodysplastic syndrome (MDS).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Talazoparib<br> | Drug: Talazoparib<br>* Maximum starting dose: 1mg/day or last tolerated dose in the originating protocol<br>* Other names: MDV3800;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4 | An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (>=) 3 times upper limit of normal (ULN); ALT or AST greater than (>) 5 times ULN; ALT or AST > 10 times ULN; ALT or AST > 20 times ULN; total TBL >2 times ULN; ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALT or AST >= 3 times ULN and TBL > 2 times ULN and ALP < 2 times ULN. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | 
| Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results >180 millimeter of mercury (mmHg) and increase from baseline >=40 mmHg, 2) absolute results <90 mmHg and decrease from baseline >30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results >110 mmHg and increase from baseline >=30 mmHg , 2) absolute results <50 mmHg and decrease from baseline >20 mmHg , 3) increase from baseline >=20 mmHg; c) Heart rate: 1) absolute results >120 beats per minute (bpm) and increase from baseline >30 bpm, 2) absolute results <50 bpm and >20 bpm decrease from baseline; d) Temperature: <=34.5 or >=38 degree Celsius. Criteria for clinically significant changes in weight: >10 percent (%) decrease from baseline. | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) |