A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

TALAPRO-1: A PHASE 2, OPEN-LABEL, RESPONSE RATE STUDY OF TALAZOPARIB IN MEN WITH DNA REPAIR DEFECTS AND METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO PREVIOUSLY RECEIVED TAXANE-BASED CHEMOTHERAPY AND PROGRESSED ON AT LEAST 1 NOVEL HORMONAL AGENT (ENZALUTAMIDE AND/OR ABIRATERONE ACETATE/PREDNISONE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03148795
• Other study ID #: MDV3800-06
• Secondary ID: C34410062016-002
• Status: Completed
• Phase: Phase 2
• Start date: July 4, 2017
• Est. completion date: March 31, 2023

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: March 31, 2023
• Est. primary completion date: September 4, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. At least 18 years of age.

2. Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features.

3. Patients must have measurable soft tissue disease per RECIST 1.1

4. DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel (testing of de novo or archival tumor tissue (via central laboratory) or prior historical testing (with Sponsor approval) using the Foundation Medicine, FoundationOne CDx™ NGS gene panel test.

5. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.

6. Serum testosterone = 1.73 nmol/L (50 ng/dL) at screening.

7. Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).

8. Progressive disease at study entry defined as 1 or more of the following 3 criteria:

• A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be = 2 µg/L (2 ng/mL) if qualifying solely by PSA progression.
• Soft tissue disease progression as defined by RECIST 1.1.
• Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan.

9. Metastatic disease.

10. Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies.

11. Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC.

12. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.

13. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

14. Estimated life expectancy of = 6 months as assessed by the investigator.

15. Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements.

16. Must use a condom when having sex from the time of the first dose of study drug through 4 months after last dose of study drug. A highly effective form of contraception must be used from the time of the first dose of study drug through 4 months after last dose of study drug when having sex with a non pregnant female partner of childbearing potential.

17. Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug.

18. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. 1. Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day 1.

2. Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy <=6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded.

3. Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within 4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during study participation

4. Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day 1.

5. Major surgery within 2 weeks before day 1.

6. Clinically significant cardiovascular disease.

7. Significant renal, hepatic, or bone marrow organ dysfunction.

8. Known or suspected brain metastasis or active leptomeningeal disease.

9. Symptomatic or impending spinal cord compression or cauda equina syndrome.

10. Prior diagnosis of myelodysplastic syndrome or acute myeloid leukemia

11. History of another cancer within 3 years before enrollment with the exception of nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor.

12. Gastrointestinal disorder affecting absorption.

13. Current or anticipated use within 7 days prior to first dose of study drug or anticipated use during the study of the following P gp inhibitors (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar).

14. Any other acute or chronic medical or psychiatric condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of data, in the opinion of the investigator or sponsor, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

15. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.

16. Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 4 months after the last dose of investigational product.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Talazoparib
1 mg daily

Locations

Country	Name	City	State
Australia	Icon Cancer Care Wesley	Auchenflower	Queensland
Australia	Eastern Clinical Research Unit	Box Hill	Victoria
Australia	Eastern Health Pathology Service	Box Hill	Victoria
Australia	Liz Plummer Cancer Care Center	Cairns	Queensland
Australia	Icon Cancer Care Chermside	Chermside	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Medical Imaging St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	St Vincent's Hospital Sydney, The Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Peninsula Health	Frankston	Victoria
Australia	Olivia Newton John Cancer Wellness & Research Centre Austin Health	Heidelberg	Victoria
Australia	Icon Cancer Care	South Brisbane	Queensland
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	Intergrated Clinical Oncology Network (ICON)	South Brisbane	Queensland
Australia	Icon Cancer Care Southport	Southport	Queensland
Australia	PRP Diagnostic Imaging	Westmead	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Ordensklinikum Linz GmbH, Elisabethinen	Linz	Upper Austria
Austria	Ordensklinikum Linz, Barmherzige Schwestern	Linz	Upper Austria
Austria	Vinzenz Pathologieverbund	Linz	Upper Austria
Austria	Paracelsus Medical University, SALK	Salzburg
Austria	Diagnosezentrum Meidling	Vienna
Austria	Isotopix-Ambulatorium fur Nuklearmedizin	Vienna
Austria	Medical University of Vienna	Vienna
Austria	Medizinische Universitat Wien	Vienna
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Algemeen Ziekenhuis Sint-Lucas	Gent
Belgium	UZ Leuven, Campus Gasthuisberg	Leuven
Brazil	Fundacao Pio XII-Hospital de Cancer de Barretos	Barretos	SAO Paulo
Brazil	Hospital de Caridade de Ijui	Ijui	RIO Grande DO SUL
Brazil	Fundacao Doutor Amaral Carvalho	Jau	SAO Paulo
Brazil	Hospital de Clinicas de Porto Alegre-HCPA	Porto Alegre	RS
France	ICO-Site Paul Papin	Angers Cedex 02
France	CHRUBesangon-H6pital Jean Minjoz	Besancon
France	Institut Bergonie, Service d'Oncologie	Bordeaux cedex
France	Centre Hospitalier Departemental Les Oudairies	La Roche sur Yon
France	Clinique Victor Hugo-Centre Jean Bernard	Le Mans Cedex 02
France	Institut de Cancerologie Strasbourg Europe	Strasbourg
France	Hopital Foch Service Oncologie	Suresnes Cedex
France	Institut Gustave Roussy	VILLEJUIF cedex
Germany	Universitaetsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Fakultat Mannheim der Universitat Heidelberg	Mannheim
Germany	Universitatsklinikum Munster	Munster
Germany	Studienpraxis Urologie	Nuertingen
Germany	Universitatsklinikum Tubingen	Tubingen
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Hungary	Orszagos Onkologiai Intezet, "C" Belgyogyaszati-Onkologiai es Klinikai Farmakogogiai Osztaly	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem	Debrecen
Hungary	Szabolcs- Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz	Nyiregyhaza
Italy	Azienda Socio Sanitaria Territoriale di Cremona (Istituti Ospitalieri di Cremona)	Cremona
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola	Forli - Cesena
Italy	AULSS3 Serenissima - Ospedale dell'Angelo - Oncologia Medica	Mestre	Venezia
Italy	SD Oncologia Clinica Sperimentale di Uro-Ginecologia	Napoli
Italy	Azienda Ospedaliero-Universitaria S. Luigi Gonzaga-SCDU Oncologia Medica	Orbassano	Torino/piemonte
Italy	IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1	Padova
Italy	Azienda Ospedaliero Universitari di Parma - U.O. Oncologia Medica	Parma
Italy	Azienda Ospedaliero Universitaria di Parma - U.O. Oncologia Medica	Parma
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Rome
Italy	Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino	Torino
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Radboud UMC	Nijmegen	THE Netherlands
Poland	Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza	Brzozow
Poland	Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Kielce
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital General Vall D'Hebron-Oncology Service	Barcelona
Spain	Hospital Universitario Quironsalud Madrid-Oncology Service	Madrid
Spain	Hospital Virgen de la Victoria	Malaga	Malga
Spain	Clinica Universidad de Navarra-Oncology Service	Pamplona	Navarra
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Instituto Valenciano de Oncologia (IVO-FINCIVO)	Valencia
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Mount Vernon Hospital	Northwood	Middlesex
United Kingdom	The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust , Sycamore House	Sutton	Surrey
United States	Levine Cancer Institute-Albermarle	Albemarle	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina
United States	Levine Cancer Institute-Pineville	Charlotte	North Carolina
United States	Levine Cancer Institute-Southpark	Charlotte	North Carolina
United States	Levine Cancer Institute-University	Charlotte	North Carolina
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	Swedish Cancer Institute Edmonds Campus	Edmonds	Washington
United States	Piedmont Cancer Institute, PC	Fayetteville	Georgia
United States	Levine Cancer Institute- Gaston	Gastonia	North Carolina
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Swedish Cancer Institute Issaquah Campus	Issaquah	Washington
United States	City of Hope-Antelope Valley	Lancaster	California
United States	Levine Cancer Institute-Lincolnton	Lincolnton	North Carolina
United States	Froedtert Hospital/Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Levine Cancer Institute-Monroe	Monroe	North Carolina
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Parkway Surgery Center	Myrtle Beach	South Carolina
United States	Weill Cornell Medical Center - New York Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical Center-New York Presbyterian Hospital	New York	New York
United States	Piedmont Cancer Institute, PC	Newnan	Georgia
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	UC Irvine Health Investigational Drug Pharmacy	Orange	California
United States	University of California, Irvine Medical Center	Orange	California
United States	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Christian Hospital North East	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center - St. Peters	Saint Peters	Missouri
United States	Medical Oncology Associates-SD	San Diego	California
United States	Sharp Outpatient Infusion Therapy Center	San Diego	California
United States	Sharp Rees-Stealy	San Diego	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Arizona Oncology Associates	Tempe	Arizona
United States	The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Medivation, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Objective Response Rate (ORR)	Best ORR was defined as the percentage of participants with best overall soft tissue response of complete response (CR) or partial response (PR) as per RECIST1.1 by an independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 millimeter (mm). Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline sum diameters.	From first dose of study drug to best overall soft tissue response CR or PR (maximum duration of 25 months)
Secondary	Time to Objective Response	Time to objective response was defined as the time from first dose of talazoparib to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per prostate cancer working Group 3 (PCWG3). Soft tissue response is defined as a best overall response of CR or PR per RECIST 1.1 by independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.	From first dose of study drug to first objective response (maximum duration of 25 months)
Secondary	Duration of Response (DOR)	DOR was defined as the time from the first objective evidence of soft tissue response (CR or PR, whichever is earlier) per RECIST 1.1 and no evidence of confirmed bone disease progression per PCWG3 to the date of first objective evidence of radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.	From the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first (maximum duration of 25 months)
Secondary	Percentage of Participants With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percentage (%)	Percentage of participants with PSA response of >= 50% was reported in this outcome measure. PSA response was calculated as a decline from baseline PSA (ng/mL) by at least 50% measured by central laboratory.	From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months)
Secondary	Percentage of Participants With Conversion of Circulating Tumor Cell (CTC) Count	Percentage of participants with conversion of CTC count was defined as percentage of participants with a CTC count >= 5 CTC per 7.5 milliliter (mL) of blood at baseline that decreased to < 5 CTC per 7.5 mL of blood any time on study.	Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months
Secondary	Percentage of Participants With a Null CTC Count	Percentage of participants with a null CTC count was defined as percentage of participants with CTC count >=1 CTC per 7.5 mL of blood at baseline that decreased to CTC = 0 per 7.5 mL of blood any time on study.	Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months
Secondary	Percentage of Participants With Baseline CTC Count <5 CTC Showed Increased CTC Counts at Any Time on Study	Percentage of participants with CTC count <5 CTC per 7.5 mL of blood at baseline those who showed an increased CTC count, compared to baseline, any time on study was reported in this study.	Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months
Secondary	Time to Prostate-Specific Antigen (PSA) Progression	Time to PSA progression was defined as the time from first dose of study treatment to the date of PSA progression, which was subsequently confirmed. The time from first dose of talazoparib to the date that a >=25% increase in PSA with an absolute increase of >=2micogram per liter (2 nanogram per mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later. Kaplan-Meier method was used for analysis.	From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months)
Secondary	Radiographic Progression-Free Survival (PFS)	Radiographic PFS was defined as the time from date of first dose of talazoparib to first objective evidence of radiographic progression as assessed in soft tissue per modified RECIST 1.1 or confirmed progression in bone per PCWG3 guidelines by independent central review or death without documented radiographic progression, whichever occurs first.	From date of first dose of study drug to first objective evidence of radiographic progression or death without documented radiographic progression, whichever occurs first (maximum duration of 25 months)
Secondary	Overall Survival (OS)	OS was defined as the time from start date (the date of first dose of treatment) to the date of death due to any cause. Participants who had not died were censored at the date of last contact. Kaplan-Meier method was used for analysis.	From first dose of study treatment up to death due to any cause during study or date of last contact (approximately 36 months)
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included both serious AEs and all non-serious AEs. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	First dose of study drug up to 28 days after last dose of study drug (study treatment was approximately for 36 months, safety follow up to approximately 37 months)
Secondary	Number of Participants With Permanent Treatment Discontinuation Due to Adverse Events	Treatment discontinuation was defined as permanent cessation of study drug treatment administration.	During study treatment (approximately up to 36 months)
Secondary	Number of Participants With Clinically Significant Abnormalities in Vital Signs	Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): absolute result greater than (>) 180 mmHg and increase from baseline greater than or equal to (>=) 40 mmHg or absolute result < 90 mmHg and decrease from baseline > 30 mmHg; 2) Diastolic blood pressure (DBP) (mmHg): absolute result > 110 mmHg and increase from baseline >= 30 mmHg or absolute result < 50 mmHg and decrease from baseline > 20 mmHg or >= 20 mmHg increase from baseline; 3) Heart rate in beats per minutes (bpm): absolute result < 50 bpm and decrease from baseline > 20 bpm or absolute result > 120 bpm and increase from baseline > 30 bpm; Weight in kilogram: > 10% decrease from baseline.	During study treatment (approximately up to 36 months)
Secondary	Number of Participants With Shift in Laboratory Parameter Values (Hematology) From Grade Less Than Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-baseline	Hematology parameters included anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, Leukocytosis and white blood cell decreased. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or non-invasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.	During study treatment (approximately up to 36 months)
Secondary	Number of Participants With Shift in Laboratory Parameter Values (Chemistry) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline	Chemistry parameters:alanine aminotransferase increased(inc), alkaline phosphatase inc, aspartate aminotransferase inc, blood bilirubin inc, chronic kidney disease, creatinine inc, gamma-glutamyl transferase (GGT) inc, hypercalcemia, Hyperglycemia, hyperkalemia, hypermagnesemia, hypocalcemia, Hyponatremia, hypoglycemia, hypokalemia, hypomagnesemia, hypernatremia, Hypoalbuminemia and hypophosphatemia. Severity was graded as Grade(G)1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G4:life-threatening consequence, urgent intervention indicated; G5: death related to AEs.	During study treatment (approximately up to 36 months)
Secondary	Number of Participants With Dose Modification	Number of participants with dose modification due to adverse events was reported.	During study treatment (approximately up to 36 months)
Secondary	Time to Deterioration in Pain Symptom Scores	Time deterioration is based on BPI-SF question 3: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours." Pain intensity was to be answered on a range of 0 to 10, where 0 corresponded to no pain and 10 worst pain. Time to this event is defined as the time from the date of first dose of study treatment to onset of pain progression, where pain progression is defined as a 2-point or more increase from baseline in the question 3 score. Kaplan-Meier method was used for analysis. Average of all assessments visits is reported in this outcome measure.	Baseline till final analysis of the outcome measure, up to maximum duration of 25 months
Secondary	Change From Baseline in Participant Reported Pain Scores Per BPI-SF Question 3	BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-SF have 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference. BPI-SF question 3 was related to participant experiencing pain at its worst in last 24 hours, score range 0 to 10, where large values corresponded to worse outcomes.	Baseline, Week 1, 3, 5, 7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Change From Baseline in European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L) Visual Analogue Scores (VAS)	The EQ-5D VAS score was a participant rated questionnaire where participants rated how they felt at assessment visit on a vertical VAS that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating a better health condition.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Number of Participants With 5 Response Levels for EQ-5D-5L Mobility Domain	EQ-5D-5L: participant rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D mobility domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Number of Participants With 5 Response Levels for EQ-5D-5L Self-Care Domain	EQ-5D-5L: participant rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D self-care domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Number of Participants With 5 Response Levels for EQ-5D-5L Usual Activity Domain	EQ-5D-5L: participant rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D usual activities domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Number of Participants With 5 Response Levels for EQ-5D-5L Pain and Discomfort Domain	EQ-5D-5L: participant rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D pain and discomfort domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Number of Participants With 5 Response Levels for EQ-5D-5L Anxiety and Depression Domain	EQ-5D-5L: participant rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D anxiety and depression domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem.	Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
Secondary	Pre-dose Plasma Concentration (Ctrough) of Talazoparib	Ctrough was defined as pre-dose plasma concentration during dosing and observed directly from data.	Pre-dose at Week 1, 5, 9 and 13
Secondary	Post-dose Plasma Concentration (Ctrough) of Talazoparib	Plasma concentration was measured 2 hours after dosing and observed directly from data.	2 hours post-dose at Week 1 and 5

External Links

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