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

NCT03148795 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: MDV3800-06C34410062016-002036-32
• Study Type: interventional
• Target: 128
• Locations: 13 countries
• Sites: 104

Brief 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).

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• Time to Objective Response

  From first dose of study drug to first objective response (maximum duration of 25 months)

• Duration of Response (DOR)

  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)

• Percentage of Participants With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percentage (%)

  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)

• Percentage of Participants With Conversion of Circulating Tumor Cell (CTC) Count

  Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months

• Percentage of Participants With a Null CTC Count

  Baseline to anytime on study during final analysis of the outcome measure, up to maximum duration of 25 months

Study Arms (1)

Talazoparib

EXPERIMENTAL

Talazoparib 1 mg daily

Drug: Talazoparib

Interventions

Talazoparib DRUG

1 mg daily

Also known as: MDV3800

Talazoparib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features.
• Patients must have measurable soft tissue disease per RECIST 1.1
• 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.
• Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
• Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.
• Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).
• 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.
• Metastatic disease.
• 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.
• 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.
• Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.

You may not qualify if:

• \. 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.
• 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.
• 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
• Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day 1.
• Major surgery within 2 weeks before day 1.
• Clinically significant cardiovascular disease.
• Significant renal, hepatic, or bone marrow organ dysfunction.
• Known or suspected brain metastasis or active leptomeningeal disease.
• Symptomatic or impending spinal cord compression or cauda equina syndrome.
• Prior diagnosis of myelodysplastic syndrome or acute myeloid leukemia
• 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.
• Gastrointestinal disorder affecting absorption.
• 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).
• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead
• Medivation, Inc.: collaborator

Study Sites (120)

Arizona Oncology Associates

Tempe, Arizona, 85284, United States

Location

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010, United States

Location

City of Hope-Antelope Valley

Lancaster, California, 93534, United States

Location

UC Irvine Health Investigational Drug Pharmacy

Orange, California, 92868, United States

Location

University of California, Irvine Medical Center

Orange, California, 92868, United States

Location

Medical Oncology Associates-SD

San Diego, California, 92123, United States

Location

Sharp Outpatient Infusion Therapy Center

San Diego, California, 92123, United States

Location

Sharp Rees-Stealy

San Diego, California, 92123, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Piedmont Cancer Institute, PC

Fayetteville, Georgia, 30214, United States

Location

Piedmont Cancer Institute, PC

Newnan, Georgia, 30265, United States

Location

Siteman Cancer Center - St. Peters

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

Christian Hospital North East

St Louis, Missouri, 63136, United States

Location

Weill Cornell Medical Center - New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Weill Cornell Medical Center-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Levine Cancer Institute-Albermarle

Albemarle, North Carolina, 28001, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Levine Cancer Institute-Pineville

Charlotte, North Carolina, 28210, United States

Location

Levine Cancer Institute-Southpark

Charlotte, North Carolina, 28211, United States

Location

Levine Cancer Institute-University

Charlotte, North Carolina, 28262, United States

Location

Levine Cancer Institute-Ballantyne

Charlotte, North Carolina, 28277, United States

Location

Levine Cancer Institute- Gaston

Gastonia, North Carolina, 28054, United States

Location

Levine Cancer Institute-Lincolnton

Lincolnton, North Carolina, 28092, United States

Location

Levine Cancer Institute-Monroe

Monroe, North Carolina, 28112, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Parkway Surgery Center

Myrtle Beach, South Carolina, 29572, United States

Location

Levine Cancer Institute-Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center

Tyler, Texas, 75701, United States

Location

Virginia Oncology Associates

Hampton, Virginia, 23666, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Swedish Cancer Institute Edmonds Campus

Edmonds, Washington, 98026, United States

Location

Swedish Cancer Institute Issaquah Campus

Issaquah, Washington, 98029, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Medical Imaging St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital Sydney, The Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

Location

PRP Diagnostic Imaging

Westmead, New South Wales, 2145, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Icon Cancer Care Wesley

Auchenflower, Queensland, 4066, Australia

Location

Liz Plummer Cancer Care Center

Cairns, Queensland, 4870, Australia

Location

Icon Cancer Care Chermside

Chermside, Queensland, 4032, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Icon Cancer Care

South Brisbane, Queensland, 4101, Australia

Location

Intergrated Clinical Oncology Network (ICON)

South Brisbane, Queensland, 4101, Australia

Location

Icon Cancer Care Southport

Southport, Queensland, 4215, Australia

Location

Eastern Clinical Research Unit

Box Hill, Victoria, 3128, Australia

Location

Eastern Health Pathology Service

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Peninsula Health

Frankston, Victoria, 3199, Australia

Location

Olivia Newton John Cancer Wellness & Research Centre Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Ordensklinikum Linz, Barmherzige Schwestern

Linz, Upper Austria, 4010, Austria

Location

Vinzenz Pathologieverbund

Linz, Upper Austria, 4010, Austria

Location

Ordensklinikum Linz GmbH, Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

Paracelsus Medical University, SALK

Salzburg, 5020, Austria

Location

Isotopix-Ambulatorium fur Nuklearmedizin

Vienna, 1090, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

Diagnosezentrum Meidling

Vienna, 1120, Austria

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Algemeen Ziekenhuis Sint-Lucas

Ghent, 9000, Belgium

Location

UZ Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Hospital de Caridade de Ijui

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital de Clinicas de Porto Alegre-HCPA

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Fundacao Pio XII-Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Fundacao Doutor Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

ICO-Site Paul Papin

Angers, 49055, France

Location

CHRUBesangon-H6pital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonie, Service d'Oncologie

Bordeaux, 33076, France

Location

Centre Hospitalier Departemental Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Clinique Victor Hugo-Centre Jean Bernard

Le Mans, 72015, France

Location

Institut de Cancerologie Strasbourg Europe

Strasbourg, 67200, France

Location

Hopital Foch Service Oncologie

Suresnes, 92151, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Essen

Essen, 45122, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Medizinische Fakultat Mannheim der Universitat Heidelberg

Mannheim, 68167, Germany

Location

Universitatsklinikum Munster

Münster, 48149, Germany

Location

Studienpraxis Urologie

Nürtingen, 72622, Germany

Location

Universitatsklinikum Tubingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Semmelweis Egyetem

Budapest, 1082, Hungary

Location

Orszagos Onkologiai Intezet, "C" Belgyogyaszati-Onkologiai es Klinikai Farmakogogiai Osztaly

Budapest, 1122, Hungary

Location

Debreceni Egyetem

Debrecen, 4032, Hungary

Location

Szabolcs- Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz

Nyíregyháza, 4400, Hungary

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli - Cesena, 47014, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, ROME, 00152, Italy

Location

Azienda Ospedaliero-Universitaria S. Luigi Gonzaga-SCDU Oncologia Medica

Orbassano, Torino/piemonte, 10043, Italy

Location

AULSS3 Serenissima - Ospedale dell'Angelo - Oncologia Medica

Mestre, Venezia, 30174, Italy

Location

Azienda Socio Sanitaria Territoriale di Cremona (Istituti Ospitalieri di Cremona)

Cremona, 26100, Italy

Location

SD Oncologia Clinica Sperimentale di Uro-Ginecologia

Napoli, 80131, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitari di Parma - U.O. Oncologia Medica

Parma, 43126, Italy

Location

Azienda Ospedaliero Universitaria di Parma - U.O. Oncologia Medica

Parma, 43126, Italy

Location

Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Radboud UMC

Nijmegen, THE Netherlands, 6525 GA, Netherlands

Location

Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza

Brzozów, 36-200, Poland

Location

Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej

Kielce, 25-734, Poland

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Virgen de la Victoria

Málaga, Malga, 29010, Spain

Location

Clinica Universidad de Navarra-Oncology Service

Pamplona, Navarre, 31008, Spain

Location

Hospital General Vall D'Hebron-Oncology Service

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Quironsalud Madrid-Oncology Service

Madrid, 28223, Spain

Location

Instituto Valenciano de Oncologia (IVO-FINCIVO)

Valencia, 46009, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Mount Vernon Hospital

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust , Sycamore House

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (2)

• Mehra N, Fizazi K, de Bono JS, Barthelemy P, Dorff T, Stirling A, Machiels JP, Bimbatti D, Kilari D, Dumez H, Buttigliero C, van Oort IM, Castro E, Chen HC, Di Santo N, DeAnnuntis L, Healy CG, Scagliotti GV. Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses. Oncologist. 2022 Oct 1;27(10):e783-e795. doi: 10.1093/oncolo/oyac172.

  PMID: 36124924 DERIVED

• de Bono JS, Mehra N, Scagliotti GV, Castro E, Dorff T, Stirling A, Stenzl A, Fleming MT, Higano CS, Saad F, Buttigliero C, van Oort IM, Laird AD, Mata M, Chen HC, Healy CG, Czibere A, Fizazi K. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol. 2021 Sep;22(9):1250-1264. doi: 10.1016/S1470-2045(21)00376-4. Epub 2021 Aug 10.

  PMID: 34388386 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 11, 2017
• Study Start: July 4, 2017
• Primary Completion: September 4, 2020
• Study Completion: March 31, 2023
• Last Updated: April 5, 2024
• Results First Posted: September 8, 2021

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (8); NL (1); FR (8); US (42); BR (4); IT (10); BE (3); PL (2); KR (5); DE (7); ES (7); GB (3); HU (4)