Testing the Safety of Different Doses of Olaparib Given Radium-223 for Men With Advanced Prostate Cancer With Bone Metastasis

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

In brief

This phase I/II trial studies the best dose and side effects of olaparib and how well it works with radium Ra 223 dichloride in treating patients with castration-resistant prostate cancer that has spread to the bone and other places in the body (metastatic). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radioactive drugs, such as radium Ra 223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Giving olaparib and radium Ra 223 dichloride may help treat patients with castration-resistant prostate cancer.

Key facts

Study ID

NCT03317392

Run by

National Cancer Institute (NCI)

People needed

132

Starts

2019-02-04

Expected to finish

2027-02-16

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Participants must be male aged >= 18 years of age
• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate
• Participants must have castrate levels of serum testosterone < 50 ng/dL
• Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist; participants receiving prior docetaxel abiraterone, or next generation AR antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease are permitted
• Participants must have progressive disease as defined by any of the following:
• Castrate resistant disease as defined by PCWG-3 criteria; participants must have a rise in PSA on two successive determination at least one week apart and PSA levels >= 2 ng/mL (only the screening PS needs to be >= 2 ng/mL) and serum testosterone < 50 ng/dL
• Soft tissue progression as defined by RECIST version 1.1
• Bone disease progression as defined by PCWG-3 criteria including the development of two or more new lesions on bone scan
• Participants must have >= 2 bone metastases by radiographic imaging and at least 1 lesion which has not been treated with prior radiation therapy
• Participants must have tumor accessible for biopsy and be agreeable to baseline tumor biopsy; a metastatic focus is preferred but if not available and prostate is still intact prostate biopsy can be performed
• Availability at the study site of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens, when available
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
• White blood cell count (WBC) >= 3,000/mcL (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days prior to administration of study treatment)
• Platelets >= 100,000/mcL (within 28 days prior to administration of study treatment)
• Hemoglobin >= 10 g/dL (transfusions permitted) (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment); for subjects with Gilbert's disease =< 3.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to administration of study treatment)
• Creatinine clearance >= 51 ml/min as defined by Cockcroft-Gault equation (within 28 days prior to administration of study treatment)
• Participants should be receiving an osteoclast targeting agent including either bisphosphonates or denosumab except in patients with contraindications as determined by the treating investigator including:
• Hypocalcemia
• Hypophosphatemia
• Renal impairment including those with a glomerular filtration rate < 35 mL/min using the Cockcroft-Gault equation
• Hypersensitivity to drug formulation
• Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of the jaw

You may not qualify if…

• Pathology consistent with small cell carcinoma of the prostate
• Presence of visceral metastases (liver, lung, brain, etc.) or malignant lymphadenopathy exceeding 4 centimeters (cm) in short diameter
• Prior treatment with radium-223
• Prior treatment with olaparib or other PARPi
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation; treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation; treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation; treatment with enzalutamide within 4 weeks of treatment initiation
• Prior hemibody external radiotherapy
• Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation
• Participants who are receiving any other investigational agents
• Imminent or established spinal cord compression based on clinical and/or imaging findings
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring need for intravenous anti-microbials, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Clinically significant medical condition defined as:
• Cerebral infarction within 6 months of study treatment
• Transient ischemic attack within 3 months of study treatment
• Myocardial infarction within 6 months of study treatment
• Uncontrolled angina within 3 months of study treatment
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months of the screening visit results in a left ventricular ejection fraction that is >= 45%
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
• Prolonged corrected QT interval by the Fridericia correction formula on the screening electrocardiogram (ECG) > 470 msec (as determined on 2 or more time points within a 24 hour period if the first ECG demonstrates a prolonged corrected QT interval) or family history of long QT syndrome
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
• Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
• History of hypertensive emergency or encephalopathy within 6 months of study treatment
• Deep venous thrombosis or pulmonary embolism within 3 months of study treatment
• Major surgery within 4 weeks of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
• Patient unable to swallow orally administered medication

Where it is running

• UC San Diego Moores Cancer Center — La Jolla, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• University of Kansas Clinical Research Center — Fairway, Kansas, United States
• University of Kansas Cancer Center — Kansas City, Kansas, United States
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
• University of Maryland/Greenebaum Cancer Center — Baltimore, Maryland, United States
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
• Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
• University of Kansas Cancer Center - North — Kansas City, Missouri, United States
• University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States
• University of Kansas Cancer Center at North Kansas City Hospital — North Kansas City, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Siteman Cancer Center-South County — St Louis, Missouri, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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