A Clinical Study Evaluating The Benefit of Adding Rucaparib to Enzalutamide for Men With Metastatic Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy

Castration-Resistant Prostate Carcinoma Clinical Trial

— CASPAR  

Official title:

CASPAR - A Phase III Trial of Enzalutamide and Rucaparib as a Novel Therapy in First-Line Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04455750
• Other study ID #: A031902
• Secondary ID: NCI-2020-02360U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 19, 2021
• Est. completion date: September 2026

Study information

• Verified date: November 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the homologous recombination DNA repair genes is helpful to decide which treatment is best for the patient.

Description:

PRIMARY OBJECTIVES:

I. To compare radiographic progression-free survival (rPFS) and overall survival (OS) with enzalutamide and rucaparib camsylate (rucaparib) versus enzalutamide alone for patients with metastatic castration resistant prostate cancer commencing first-line therapy.

II. (PK substudy) To evaluate the safety and tolerability of rucaparib and enzalutamide combination III. (Quality of life substudy) To compare quality of life as measured by FACT-P Trial Outcome Index in patients with mCRPC who receive enzalutamide plus rucaparib vs enzalutamide alone at the 12-month time point (primary QOL timepoint).

SECONDARY OBJECTIVES:

I. To compare rPFS and OS with enzalutamide and rucaparib versus enzalutamide alone within homologous-recombination repair (HRR) aberrant and wild-type patients.

II. To evaluate the effects of concurrent administration of rucaparib on time to unequivocal clinical progression.

III. To evaluate the effects of concurrent administration of rucaparib on best radiographic response using Prostate Cancer Working Group 3 (PCWG3) criteria.

IV. To evaluate the effects of concurrent administration of rucaparib on duration of overall response.

V. To evaluate the effects of concurrent administration of rucaparib on prostate specific antigen (PSA) response rate.

VI. To evaluate the effects of concurrent administration of rucaparib on best response by serum PSA by months 7 and 13.

VII. To evaluate the effects of concurrent administration of rucaparib on time to first symptomatic skeletal event (SSE).

VIII. To evaluate the effects of concurrent administration of rucaparib on safety and tolerability as measured by National Cancer Institute (NCI) Common Toxicity Criteria; and trial discontinuation for treatment emergent toxicities.

IX. To compare performance of plasma-based and tissue-based genomic profiling in detection of homologous-recombination repair mutation (HRRm) in metastatic castration-resistant prostate cancer (mCRPC).

OUTLINE:

In the randomized, placebo-controlled phase III study, patients will be randomized to 1 of 2 arms:

ARM I: Patients will receive enzalutamide orally (PO) once daily (QD) and rucaparib PO twice daily (BID). Patients who did not undergo bilateral orchiectomy will also receive androgen deprivation therapy (ADT) consisting of leuprolide acetate intramuscularly (IM), goserelin acetate subcutaneously (SC) every 12 weeks or degarelix SC. Cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients will receive enzalutamide PO QD and placebo PO BID. Patients who did not undergo bilateral orchiectomy will also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients will be followed every 3 months for 2 years, then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 61
• Est. completion date: September 2026
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic/cytologic documentation of prostate adenocarcinoma

• Adequate archival tumor specimen or archival slides must be available to be tested as part of the trial screening (most recent metastatic site biopsy preferred, but primary prostate biopsy allowed if metastatic biopsy is not available or inadequate. A new biopsy is not required for pre-registration in the trial as long as sufficient archival tissue is available). Due to significant variability between tests, results from an existing targeted next-generation exome sequencing test may not be used for this trial

• Progressive disease must be demonstrated at study entry while the patient is on continuous androgen deprivation therapy (ADT) or status post orchiectomy. Progressive disease is defined as one or more of the following criteria:

• PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 1.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy (>=4 weeks since last flutamide, bicalutamide or nilutamide, apalutamide or darolutamide)

• Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue lesions

• Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria

• Measurable or non-measurable metastatic disease

• No prior therapy for metastatic castration-resistant prostate cancer, defined as a treatment given for prostate cancer with radiographically-detectable metastasis and a serum testosterone level less than 50 ng/dl (1.73 nmol/L) at the time of registration

• >= 2 weeks or 5 half-lives (whichever is shorter) since prior therapy with flutamide, dutasteride, bicalutamide, niltamide, finasteride, aminoglutethimide, estrogens, cytoproterone, chemotherapy, abiraterone, apalutamide, or darolutamide

• >= 4 weeks or 5 half-lives (whichever is shorter) since any prior investigational therapy

• >= 4 weeks since a major surgery or radiation

• No prior therapy with enzalutamide, rucaparib or any other PARP inhibitor, or platinum chemotherapy

• Prior docetaxel and/or novel anti-androgen use is allowed only if given in the hormone-sensitive non-metastatic or metastatic, or castration-resistant non-metastatic disease setting

• Patient must have discontinued all previous treatments for cancer (except ADT and bone anti-responsive therapies such as denosumab or zoledronic acid) and must have recovered from all acute side effects of prior therapy or surgical procedures to =< grade 1 or baseline prior to randomization, with the exception of fatigue, alopecia or peripheral neuropathy

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 10 g/dL

• Serum testosterone =< 50 ng/dl (=< 1.73 nmol/L)

• Serum creatinine =< 1.5 x upper limit of normal (ULN)

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Aspartate transaminase (AST)/alanine transferase (ALT) =< 2.5 x upper limit of normal (ULN)

• No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long (1) as the metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND (2) the patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND (3) the patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to pre-registration

• No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies

• No blood product transfusion, granulocyte/granulocyte-macrophage-colony stimulating factor (G-CSF/GM-CSF), or erythropoietin/thrombopoietin use within 14 days of pre-registration

• No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months

• No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years

• No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction

• No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of registration

• No planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery

• No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression

• No known or suspected contraindications or hypersensitivity to enzalutamide, rucaparib, or to any of the excipients

• No known or suspected gastrointestinal disorder affecting absorption of oral medications

• No prior malignancy for which the last treatment was given within the past 2 years, or any active concurrent malignancy with the exception of non-melanomatous localized skin cancers (such as squamous or basal cell carcinoma of the skin)

• Any concomitant medications that are strong inhibitors of CYP2C8 or inducers of CYP3A4 cytochrome enzymes must be discontinued prior to registration. Dose adjustments per Food and Drug Administration (FDA) label or clinical judgement should be considered for any concomitant medications that are moderate inhibitors of CYP2C8 or inducers of CYP3A4 cytochrome enzymes

• Any concomitant medications that are substrates of CYP3A4, CYP2C9 and CYP2C19 cytochrome enzymes should be monitored closely per clinical judgement of the treating physician

Related Conditions & MeSH terms

• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Adenocarcinoma
• Prostatic Neoplasms
• Stage IV Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8
• Stage IVB Prostate Cancer AJCC v8

Intervention

Drug:
• Enzalutamide
Given PO
• Rucaparib camsylate
Given PO
• Placebo
Given PO
• Leuprolide Acetate
Given IM
• Goserelin Acetate
Given SC
• Degarelix
Given SC

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Hickman Cancer Center	Adrian	Michigan
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Augusta Oncology Associates PC-D'Antignac	Augusta	Georgia
United States	Augusta Oncology Associates PC-Wheeler	Augusta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	FHCC Overlake	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Wake Forest University at Clemmons	Clemmons	North Carolina
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Kaiser Permanente Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Glens Falls Hospital	Glens Falls	New York
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Queens Hospital Center	Jamaica	New York
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Sparrow Hospital	Lansing	Michigan
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Nyack Hospital	Nyack	New York
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Reid Health	Richmond	Indiana
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	West Suburban Medical Center	River Forest	Illinois
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Sharp Memorial Hospital	San Diego	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	FHCC at Northwest Hospital	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Northbay Cancer Center	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Veterans Affairs Connecticut Healthcare System-West Haven Campus	West Haven	Connecticut
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Wake Forest Baptist Health - Wilkes Medical Center	Wilkesboro	North Carolina
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan
United States	Avera Cancer Institute at Yankton	Yankton	South Dakota
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of life	Measured by change from baseline to 12 months of the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) patient-reported outcome questionnaire.	12 months
Other	Quality of life	Measured by change from baseline to 12 months of the Utility Score of the European Quality of Life Five Dimension Five Level (EQ-5D-5L) patient-reported outcome questionnaire.	12 months
Other	Laboratory correlative science	Area under curve for plasma-based and tissue-based genomic profiling in detection of HRRm in mCRPC.	Up to 1 year after completion of treatment
Other	Laboratory correlative science	The proportion of patients with homologous-recombination repair (HRR) alterations at baseline who develop HRR reversion/function restoring alterations after initiation of treatment in each arm with a chi-square test (or Fisher's exact test if more appropriate).	Up to 1 year after completion of treatment
Primary	Radiographic progression-free survival (rPFS)	Radiographic progression-free survival (rPFS) is defined as the time from randomization to date of disease progression or death due to any cause. rPFS time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 5 years post treatment
Primary	Overall survival (OS)	Overall survival is defined as the time from randomization to death due to any cause. Overall survival time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 5 years post treatment
Secondary	Radiographic progression-free survival (rPFS) within HRRm status	Defined as the time from randomization to date of disease progression or death due to any cause. rPFS time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 5 years post treatment
Secondary	Time to unequivocal clinical progression	Defined as deterioration in clinical status clearly attributable to prostate cancer progression with occurrence of cancer pain requiring initiation of chronic administration of opiate analgesia, or an immediate need to re-initiate cytotoxic chemotherapy, radiation therapy or surgical intervention for disease-progression related events; or deterioration of Eastern Cooperative Oncology Group (ECOG) performance status to 3 or greater. Time to unequivocal clinical progression will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 5 years post treatment
Secondary	Overall survival by HRRm status	Defined as the time from randomization to death due to any cause.Overall survival time will be compared between the treatment arms using a stratified (by HRRm status) log-rank test. Median times per treatment arms/HRRm status will be reported.	Up to 5 years post treatment
Secondary	Overall response rate	Defined as confirmed radiographic complete response or partial response. The proportion of patients with confirmed radiographic response or partial response will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).	Up to 1 year after completion of treatment
Secondary	Duration of overall response	Defined as the time from documentation of a radiographic response to disease progression. Duration of response time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 1 year after completion of treatment
Secondary	Prostate specific antigen (PSA) response rate	Defined as >= 50% reduction in PSA from baseline. The proportion of patients with PSA response will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).	Up to 1 year after completion of treatment
Secondary	Best response by serum prostate specific antigen (PSA)	Defined as best percentage PSA decline from baseline to 7 and 13 months. The percent PSA decline will be compared between treatment arms with a Wilcoxon rank sum test.	At 7 and 13 months from the start of treatment
Secondary	Time to first symptomatic skeletal event (SSE)	Defined as the time to first use of external-beam radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or nonvertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention. Time to first SSE will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.	Up to 5 years after completion of treatment
Secondary	Incidence of adverse events	Frequency as measured by National Cancer Institute (NCI) Common Toxicity Criteria. The proportion of patients experiencing at least one grade 3+ adverse event will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).	Up to 1 year after completion of treatment
Secondary	Discontinuation for treatment emergent toxicities	The proportion of patients who discontinued treatment for emergent toxicities will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).	Up to 1 year after completion of treatment