Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC

mCRPC Clinical Trial

— TALAPRO-2  

Official title:

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TALAZOPARIB WITH ENZALUTAMIDE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03395197
• Other study ID #: C3441021
• Secondary ID: 2017-003295-31TA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 18, 2017
• Est. completion date: December 31, 2025

Study information

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

Clinical Trial Summary

This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.

Description:

Part 1 is an open-label, non-randomized, safety and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK at select sites. Part 2 is a randomized, double-blind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide in patients with mCRPC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1054
• Est. completion date: December 31, 2025
• Est. primary completion date: October 3, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be < 4).

For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status

Consent to a saliva sample collection for a germline comparator unless prohibited by local regulations or ethics committee decision (optional for patients in Part 1).

Surgically or medically castrated, with serum testosterone = 50 ng/dL (= 1.73 nmol/L) at screening.

Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan.

Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria:

• Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 consecutive assessments with an interval of at least 7 days between assessments..

• Soft tissue disease progression as defined by RECIST 1.1.

• Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan.

Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or randomization (Part 2) is allowed but not mandatory.

Eastern Cooperative Oncology Group (ECOG) performance status = 1.

Life expectancy = 12 months as assessed by the investigator.

Able to swallow the study drug and have no known intolerance to study drugs or excipients.

Must agree to use a condom when having sex with a partner from the time of the first dose of study drug through 4 months after last dose of study treatment. Must also agree for female partner of childbearing potential to use an additional highly effective form of contraception from the time of the first dose of study treatment through 4 months after last dose of study treatment when having sex with a non pregnant female partner of childbearing potential.

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

Evidence of a personally signed and dated informed consent document (and molecular prescreening consent if appropriate) indicating that the patient [or a legally acceptable representative/legal guardian] has been informed of all pertinent aspects of the study.

Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

Any prior systemic cancer treatment initiated in in the non metastatic CRPC and mCRPC disease state.

Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.

Prior treatment with second-generation androgen receptor inhibitors (enzalutamide, apalutamide, and darolutamide), a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.

Prior treatment with platinum-based chemotherapy within 6 months (from the last dose) prior to Day 1 (Part 1) or randomization (Part 2), or any history of disease progression on platinum-based therapy within 6 months (from the last dose).

Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel T, or radionuclide therapy received in the castration-sensitive prostate cancer is NOT exclusionary if discontinued in the 28 days prior to Day 1 (Part 1) or randomization (Part 2).

Treatment with any investigational agent within 4 weeks before Day 1 (Part 1) or randomization (Part 2).

Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization (Part 2).

Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or randomization (Part 2).

Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or randomization (Part 2), or palliative localized radiation therapy within 3 weeks before randomization (Part 2).

Clinically significant cardiovascular disease

Significant renal dysfunction as defined by any of the following laboratory abnormalities:

• Renal: eGFR < 30 mL/min/1.73 m2 by the MDRD equation (available via www.mdrd.com).

Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) at screening.

Significant hepatic dysfunction as defined by any of the following laboratory abnormalities on screening labs:

• Total serum bilirubin >1.5 times the upper limit of normal (ULN) (>3 × ULN for patients with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times ULN (>5 × ULN if liver function abnormalities are due to hepatic metastasis).

• Albumin <2.8 g/dL

Absolute neutrophil count < 1500/µL, platelets < 100,000/µL, or hemoglobin < 9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology values at screening).

Known or suspected brain metastasis or active leptomeningeal disease.

Symptomatic or impending spinal cord compression or cauda equina syndrome.

Any history of myelodysplastic syndrome, acute myeloid leukemia, or prior malignancy except any of the following:

• Carcinoma in situ or non melanoma skin cancer

• Any prior malignancies =3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage.

• Stage 0 or Stage 1 cancer <3 years before randomization that has a remote probability of recurrence or progression in the opinion of the investigator

Gastrointestinal disorder affecting absorption.

Fertile male subjects who are unwilling or unable to use highly effective methods of contraception for the duration of the study and for 4 months after the last dose of investigational product.

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.

Other acute or chronic medical (concurrent disease, infection, or comorbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that interferes with ability to participate in the study, 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.

History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of randomization (Part 2).

Related Conditions & MeSH terms

• mCRPC

Intervention

Drug:
• Talazoparib with enzalutamide
Talazoparib 0.5 mg/day plus enzalutamide 160mg/day
• Placebo with enzalutamide
Placebo plus enzalutamide 160 mg/day

Locations

Country	Name	City	State
Argentina	Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" Cemic	Caba
Argentina	Hospital Británico de Buenos Aires	Caba
Argentina	Clinica Universitaria Reina Fabiola	Cordoba
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Centro de Investigacion Pergamino SA - Clinica Pergamino SA	Pergamino	Buenos Aires
Argentina	Instituto de Oncologia de Rosario	Rosario	Santa FE
Australia	ICON Cancer Centre Wesley	Auchenflower	Queensland
Australia	River City Pharmacy	Auchenflower	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	ICON Cancer Centre Chermside	Chermside	Queensland
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre	North Melbourne	Victoria
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	ICON Cancer Centre South Brisbane	South Brisbane	Queensland
Australia	Integrated Clinical Oncology Network Pty Ltd (ICON)	South Brisbane	Queensland
Australia	ICON Cancer Centre Southport	Southport	Queensland
Belgium	AZ Klina	Brasschaat
Belgium	A.Z. Sint-Lucas	Gent
Belgium	UZ Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	Clinique Saint-Pierre Ottignies	Ottignies
Belgium	CHU UCL Namur site Godinne	Yvoir
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	SP
Brazil	Associacao Hospital de Caridade de Ijui	Ijui	RS
Brazil	Sociedade Beneficencia e Caridade de Lajeado - Hospital Bruno Born	Lajeado	RS
Brazil	Centro de Pesquisa Clinica em Oncologia - Hospital Sao Lucas da Pontificia Universidade Catolica	Porto Alegre	RS
Brazil	Centro Gaucho Integrado - Hospital Mae de Deus	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao - Grupo Hospitalar Conceicao	Porto Alegre	RS
Brazil	MedPlex Eixo Norte	Porto Alegre	RS
Brazil	Hospital CopaDor	Rio de Janeiro	RJ
Brazil	Hospital Gloria D'Or	Rio de Janeiro	RJ
Brazil	Hospital Universitario Pedro Ernesto-Centro de Pesquisas (CEPUSA)	Rio de Janeiro	RJ
Brazil	Instituto D'Or de Pesquisa e Ensino	Rio de Janeiro	RJ
Brazil	Instituto Nacional de Câncer José de Alencar Gomes da Silva - INCA	Rio de Janeiro	RJ
Brazil	Instituto Nacional de Câncer José de Alencar Gomes da Silva - INCA	Rio de Janeiro	RJ
Brazil	Oncologia D'Or	Rio de Janeiro	RJ
Brazil	Oncologia D'Or	Rio de Janeiro	RJ
Brazil	Faculdade de Medicina do ABC - Centro de Estudos e Pesquisa de Hematologia e Oncologia (CEPHO)	Santo Andre	SP
Brazil	Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Oncologia (CEPHO)	Santo Andre	SP
Brazil	Hospital Alemão Oswaldo Cruz	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo-ICESP-Nucleo de Pesquisa	Sao Paulo	SP
Canada	Tom Baker Cancer Centre - Alberta Health Services	Calgary	Alberta
Canada	Centre integre universitaire de sante et de services sociaux du Saguenay-Lac-Saint-Jean	Chicoutimi	Quebec
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Center	Ottawa	Ontario
Canada	Centre integre universitaire de sante et de services sociaux de l'Estrie	Sherbrooke	Quebec
Chile	James Lind Centro de lnvestigacion del Cancer	Araucania
Chile	Sociedad Prosalud Montes y Orlandi Ltda. Fantasy name (Orlandi Oncologia)	Santiago	Metropolitana
Chile	Centro de Investigacion Clinica del Sur	Temuco	Region DE LA Araucania
Chile	Sociedad de Investigaciones Medicas Ltda (SIM)	Temuco	Region DE LA Araucania
Chile	Sociedad de Investigaciones Medicas Ltda (SIM)	Temuco	Region DE LA Araucania
Chile	Centro de Investigaciones Clinicas Vina del Mar	Vina del Mar	Valparaiso
Chile	Centro de Investigaciones Clinicas Vina del Mar	Vina del Mar	Valparaiso
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing
China	Peking University First Hospital / Urology Department	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Jilin Province Tumor Hospital	Changchun	Jilin
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing University Cancer Hospital	Chongqing
China	The First Affiliated Hospital Of Fujian Medical University	Fuzhou	Fujian
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	The First affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The First People's Hospital of Lianyungang	Lianyungang	Jiangsu
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Ningbo First Hospital	Ningbo	Zhejiang
China	The first affiliated hospital of Ningbo University	Ningbo	Zhejiang
China	Fudan University Cancer Hospital, Deptartment of Urology	Shanghai
China	Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai
China	The Fifth People's Hospital of Shanghai, Fudan University	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Second Affiliated Hospital of Suzhou University	Suzhou	Jiangsu
China	Second Affiliated Hospital of Suzhou University	Suzhou	Jiangsu
China	The Second Hospital of Tianjin Medical University	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	The First Affiliated Hosptial of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital, Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	First Affiliated Hospital of Xiamen University	Xiamen	Fujian
Czechia	Fakultní nemocnice Hradec Králové	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava-Poruba
Czechia	Multiscan s.r.o.	Pardubice
Czechia	Fakultní nemocnice Královské Vinohrady	Praha 10
Finland	Docrates Cancer Center	Helsinki
Finland	HUS Helsinki University Hospital	Helsinki
Finland	OYS apteekki	Kempele
Finland	Kuopio University Hospital	Kuopio
Finland	Kuopio University Hospital	Kuopio
Finland	Oulun yliopistollinen sairaala	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
France	Centre d'Oncologie du Pays-Basque	Bayonne
France	Clinique Ramsay Belharra	Bayonne
France	Hopital Saint Andre - CHU de Bordeaux	Bordeaux
France	CHD Vendée	LA ROCHE SUR YON cedex 9
France	Centre de cancerologie de la Sarthe	Le Mans
France	Clinique Victor Hugo	Le Mans
France	Clinique Victor Hugo-Centre Jean Bernard	Le Mans
France	Centre Leon Berard	Lyon Cedex 08
France	Centre Léon Bérard	Lyon CEDEX 08
France	CHU Montpellier-Hopital Saint Eloi	Montpellier cedex 5
France	Hopital Saint-Louis	Paris
France	Hopital Europeen Georges Pompidou	Paris Cedex 15
France	Clinique Sainte Anne	Strasbourg
France	Hopitaux Universitaires de Strasbourg - ICANS	Strasbourg
France	Hopital Foch	Suresnes
France	Hopital Foch	Suresnes Cedex
France	Institut Gustave Roussy	VILLEJUIF cedex
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinik Heidelberg	Heidelberg
Germany	Diagnostikzentrum	Kirchheim
Germany	Universitaetsklinikum Muenster	Muenster
Germany	Studienpraxis Urologie	Nuertingen
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem Urologiai Klinika	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Uzsoki Utcai Kórház	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont Onkoterapias Intezet	Pecs
Israel	Rambam Health Care Campus	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliero-Universitaria Policlinico Sant' Orsola Malpighi	Bologna	BO
Italy	ASST di Cremona	Cremona	CR
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS	Meldola	FC
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale - Napoli	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano	TO
Italy	Azienda Ospedaliera S. Maria	Terni	TN
Italy	Ospedale Santa Chiara	Trento	TN
Japan	Chiba Cancer Center	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hamamatsu University School of Medicine, University Hospital	Hamamatsu	Shizuoka
Japan	Hirosaki University School of Medicine & Hospital	Hirosaki	Aomori
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto
Japan	National Hospital Organization Kure Medical Center and Chugoku Cancer Center	Kure	Hiroshima
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	National Hospital Organization Tokyo Medical Center	Meguro-ku	Tokyo
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka International Cancer Institute	Osaka-shi	Osaka
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Osaka University Hospital	Suita	Osaka
Japan	Tokushima University Hospital	Tokushima
Japan	Yamagata Prefectural Central Hospital	Yamagata
Japan	Yamagata University Hospital	Yamagata
Japan	Yokohama City University Medical Center	Yokohama	Kanagawa
Japan	Yokosuka Kyosai Hospital	Yokosuka	Kanagawa
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Clinical Trial Pharmacy, National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Cancer Center Clinical Trial, Asan Medical Center	Seoul
Korea, Republic of	Clinical Trial Pharmacy, The Catholic University of Korea	Seoul
Korea, Republic of	Clinical Trials Center Pharmacy	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
New Zealand	Auckland City Hospital	Auckland
New Zealand	Canterbury District Health Board	Christchurch	Canterbury
New Zealand	Waikato Hospital	Hamilton	Waikato
New Zealand	Tauranga Urology Research Limited	Tauranga	BAY OF Plenty
Norway	Ostfold County Hospital, Kalnes	Gralum
Norway	Sykehusapoteket Ostfold, Kalnes	Gralum
Norway	Akershus University Hospital	Lorenskog
Norway	Oslo University Hospital -Ullevål & Radiumhospitalet	Oslo
Norway	St. Olavs Hospital, Trondheim University Hospital	Trondheim
Peru	Clinica Monte Carmelo S.C.R.LTDA.	Arequipa
Peru	Clinica Internacional Sede San Borja	Lima
Peru	Clinica Oncosalud	Lima
Peru	Hospital Militar Central "Coronel Luis Arias Schreiber"	Lima
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza	Brzozow
Poland	Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii	Gdynia
Poland	Przychodnia Lekarska "Komed" Roman Karaszewski	Konin
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina	Otwock
Poland	City Clinic Sp. z o.o.	Warszawa
Poland	NZOZ Szpital Mazovia; Oddzial urologiczny	Warszawa
Portugal	Centro Clínico Académico - Braga, Associação (2CABraga)	Braga
Portugal	Instituto Português Oncologia de Coimbra Francisco Gentil - E.P.E	Coimbra
Portugal	Fundação Champalimaud	Lisboa
Portugal	Hospital da Luz Lisboa	Lisboa
Portugal	Centro Hospitalar do Porto - Hospital de Santo Antonio	Porto
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil	Porto
South Africa	Cancercare Rondebosch Oncology	Cape Town	Western CAPE
South Africa	Outeniqua Cancercare Oncology Unit	George	Western CAPE
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Wits Clinical Research	Johannesburg
South Africa	Wits Clinical Research	Johannesburg	Gauteng
South Africa	Wits Clinical Research Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), Clinical Trial Site	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials	Kraaifontein, Cape Town	Western CAPE
South Africa	Wits Clinical Research	Parktown	Gauteng
South Africa	Cancercare Langenhoven Drive Oncology Centre	Port Elizabeth	Eastern CAPE
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Institut Catala d'Oncologia - ICO L'Hospitalet	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Corporacio Sanitaria i Universitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela	A Coruna
Sweden	Klinisk Provningsenhet (KPE) Onkologi	Goteborg
Sweden	Patientomrade Backencancer, Tema Cancer	Stockholm
Sweden	Cancercentrum	Umeå
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral
United Kingdom	Royal Cornwall Hospitals NHS Trust	Cornwall
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	The Clatterbridge Cancer Centre - Liverpool	Liverpool
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Imperial College Healthcare NHS Trust, Charing Cross Hospital	London
United Kingdom	Oxford University Hospitals NHS Trust	Oxford
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth	Devon
United States	Urology Group of New Mexico	Albuquerque	New Mexico
United States	Florida Cancer Specialists	Altamonte Springs	Florida
United States	UPMC Hillman Cancer Center - Altoona	Altoona	Pennsylvania
United States	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	University of Colorado Denver CTO/CTRC	Aurora	Colorado
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	University of Colorado Hospital- Anschutz Inpatient Pavilion	Aurora	Colorado
United States	University of Colorado Hospital- Anschutz Outpatient Pavilion	Aurora	Colorado
United States	Urology Austin PLLC	Austin	Texas
United States	Clara Maass Medical Center	Belleville	New Jersey
United States	New Jersey Cancer Care and Blood Disorders	Belleville	New Jersey
United States	UPMC Hillman Cancer Center - Upper St. Clair	Bethel Park	Pennsylvania
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Florida Cancer Specialists	Brandon	Florida
United States	Montefiore Medical Center - Montefiore Medical Park	Bronx	New York
United States	AdventHealth Medical Group Hematology & Oncology at Celebration	Celebration	Florida
United States	Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers	Chandler	Arizona
United States	Sarah Cannon Research Institute	Chattanooga	Tennessee
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Cook County Health (CCH)	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County/IND Pharmacy	Chicago	Illinois
United States	Sharp Rees-Stealy	Chula Vista	California
United States	South County Hematology/Oncology	Chula Vista	California
United States	TriState urologic Services PSC Inc., dba The Urology Group	Cincinnati	Ohio
United States	Kaiser Sunnyside Medical Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Florida Cancer Specialists	Clearwater	Florida
United States	Tennesse Oncology, PLLC	Cleveland	Tennessee
United States	Florida Cancer Specialists	Daytona Beach	Florida
United States	The Urology Center of Colorado	Denver	Colorado
United States	Rio Grande Urology, P.A.	El Paso	Texas
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Inova Schar Cancer Institute Infusion Pharmacy	Fairfax	Virginia
United States	The University of Kansas Clinical Research Center	Fairway	Kansas
United States	Farmington Health Center -University of Utah	Farmington	Utah
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Piedmont Cancer Institute	Fayetteville	Georgia
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Florida Cancer Specialists	Gainesville	Florida
United States	Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers	Gilbert	Arizona
United States	Glendale Adventist Medical Center	Glendale	California
United States	Marin Cancer Care, Inc.	Greenbrae	California
United States	UPMC Hillman Cancer Center - Arnold Palmer - Mt View	Greensburg	Pennsylvania
United States	Kaiser Westside Medical Center	Hillsboro	Oregon
United States	AMITA Health Adventist Medical Center Hinsdale	Hinsdale	Illinois
United States	AMITA Health Cancer Institute	Hinsdale	Illinois
United States	Houston Metro Urology	Houston	Texas
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Clark Memorial Hospital Radiology	Jeffersonville	Indiana
United States	First Urology, PSC	Jeffersonville	Indiana
United States	AdventHealth Medical Group Hematology & Oncology at Kissimmee	Kissimmee	Florida
United States	Cancer Center Oncology Medical Group	La Mesa	California
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Keystone Urology Specialists	Lancaster	Pennsylvania
United States	Florida Cancer Specialists	Largo	Florida
United States	Florida Cancer Specialists	Lecanto	Florida
United States	Loma Linda University Cancer Center - Hematology/Oncology Clinic	Loma Linda	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	VA Long Beach Healthcare System	Long Beach	California
United States	UCLA Clark Urology Center	Los Angeles	California
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers	Mesa	Arizona
United States	Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers	Mesa	Arizona
United States	Clinical Research Solutions	Middleburg Heights	Ohio
United States	UPMC Hillman Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	The Vanderbilt Clinic	Nashville	Tennessee
United States	Urology Associates P.C.	Nashville	Tennessee
United States	Vanderbuilt University Medical Center, Department of Urology	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Florida Cancer Specialists	New Port Richey	Florida
United States	Providence Cancer Institute Newberg Clinic	Newberg	Oregon
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Piedmont Cancer Institute	Newnan	Georgia
United States	Southeastern Regional Medical Center	Newnan	Georgia
United States	University Radiology	Nutley	New Jersey
United States	Florida Cancer Specialists	Ocala	Florida
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	GU Research Network/Urology Cancer Center	Omaha	Nebraska
United States	University of California, Irvine Medical Center	Orange	California
United States	Florida Cancer Specialists	Orange City	Florida
United States	Providence Cancer Institute Willamette Falls	Oregon City	Oregon
United States	AdventHealth Orlando	Orlando	Florida
United States	Florida Cancer Specialists	Orlando	Florida
United States	Investigational Drug Services, Advent Health Orlando	Orlando	Florida
United States	Stanford Cancer Institute	Palo Alto	California
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center - Passavant (HOA)	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center - Passavant (OHA)	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Providence Cancer Institute Franz Clinic	Portland	Oregon
United States	Providence Oncology and Hematology Care Clinic - Westside	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	Desert Hematology Oncology Medical Group, Incorporation	Rancho Mirage	California
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Urology Austin, PLLC	Round Rock	Texas
United States	VA Saint Louis Healthcare System	Saint Louis	Missouri
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Redwood Health Center-University of Utah	Salt Lake City	Utah
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah
United States	Medical Oncology Associates-SD	San Diego	California
United States	Sharp Memorial Hospital Investigational Pharmacy	San Diego	California
United States	Sharp Rees-Stealy	San Diego	California
United States	Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	UPMC Hillman Cancer Center - Northwest	Seneca	Pennsylvania
United States	South Jordan Health Center -University of Utah	South Jordan	Utah
United States	Florida Cancer Specialists	Spring Hill	Florida
United States	Stanford Health Care	Stanford	California
United States	Florida Cancer Specialists	Stuart	Florida
United States	Associated Medical Professionals of New York, PLLC	Syracuse	New York
United States	Florida Cancer Specialists	Tampa	Florida
United States	Florida Cancer Specialists	Tavares	Florida
United States	Baylor Scott & White Medical Center - Temple	Temple	Texas
United States	Florida Cancer Specialists	The Villages	Florida
United States	Arizona Urology Specialists	Tucson	Arizona
United States	Arizona Urology Specialists	Tucson	Arizona
United States	UPMC Hillman Cancer Center - Uniontown	Uniontown	Pennsylvania
United States	Florida Cancer Specialists	Vero Beach	Florida
United States	New Jersey Urology, LLC	Voorhees	New Jersey
United States	UPMC Hillman Cancer Center - Washington	Washington	Pennsylvania
United States	Florida Cancer Specialists	Wellington	Florida
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	The University of Kansas Cancer Center	Westwood	Kansas
United States	Florida Cancer Specialists	Winter Park	Florida
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Norway,  Peru,  Poland,  Portugal,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1	An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per Common Terminology Criteria for Adverse Events (CTCAE) version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. Serious TEAE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to Day 66 in Part 1
Primary	Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by Preferred Term (PT) and Max CTCAE Grade Occuring Within the First 66 Days of Dosing - Part 1	An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1=mild AE; Grade 2=moderate AE; Grade 3=severe AE; Grade 4=life-threatening or disabling AE; Grade 5=death related to an AE. Medical Dictionary for Regulatory Activities (MedDRA) v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with at least 1 occurrence in participants are reported for this outcome measure. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to Day 66 in Part 1
Primary	Number of Participants With All-Causality TEAEs During the Overall Period of Part 1	An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. Serious TEAE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Primary	Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1	An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Primary	Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1	An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1=mild AE; Grade 2=moderate AE; Grade 3=severe AE; Grade 4=life-threatening or disabling AE; Grade 5=death related to an AE. MedDRA v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with at least 1 occurrence in participants are reported for this outcome measure. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Primary	Number of Participants With Treatment-Related Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade in >=10% of Participants Occuring Anytime After Dosing - Part 1	An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are newly occurring AEs or those worsening after first dose. Treatment-related AE was any AE attributed to study intervention in a participant who received study intervention. As per CTCAE version 4, Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; Grade 5=death related to an AE. MedDRA v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with incidence in >=10% of participants are reported. Results as of 16 Aug 2022 are reported.	Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Primary	Blinded Independent Central Review (BICR) Assessed Radiographic Progression-Free Survival (rPFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for All-Comers - Part 2 Cohort 1	rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per RECIST 1.1, or death, whichever occurs first. Soft tissue disease status was assessed at regular intervals during the course of the study by computed tomography (CT) of chest and CT or magnetic resonance imaging (MRI) of abdomen and pelvis. Progression is defined using RECIST 1.1 as a >=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Results as of 16 Aug 2022 are reported for this outcome measure.	From the start of treatment to the time of first documented progression, or death (maximum up to 42 months)
Primary	BICR Assessed rPFS Per RECIST 1.1 in Patients With DDR Deficiencies - Part 2	rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per RECIST 1.1, or death, whichever occurs first. Soft tissue disease status was assessed at regular intervals during the course of the study by CT of chest and CT or MRI of abdomen and pelvis. Results as of 03 Oct 2022 are reported for this outcome measure.	From the start of treatment to the time of first documented progression, or death (maximum up to 38 months)

External Links

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