Different Doses of Olaparib Given With Radium-223 in Men With Advanced Prostate Cancer With Bone Metastasis
A Phase 1/2 Study of Combination Olaparib and Radium-223 in Men With Metastatic Castration-Resistant Prostate Cancer With Bone Metastases (COMRADE)
3 other identifiers
interventional
132
1 country
22
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2019
Longer than P75 for phase_1
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 20, 2017
CompletedFirst Posted
Study publicly available on registry
October 23, 2017
CompletedStudy Start
First participant enrolled
February 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2025
CompletedResults Posted
Study results publicly available
May 5, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 16, 2027
ExpectedMay 5, 2026
April 1, 2026
6.2 years
October 20, 2017
March 24, 2026
April 15, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Phase I: Maximum Tolerated Dose
Determine the maximum tolerated dose (MTD) of olaparib in combination with radium Ra 223 dichloride (radium-223). (Phase I)
56 days
Phase II: Radiographic Progression-free Survival (rPFS)
Radiographic progression is defined by Prostate Cancer Working Group 3 criteria for bone metastases and RECIST version 1.1 for non-bone metastases. Median rPFS will be estimated using the Kaplan-Meier method by treatment arm. A stratified Cox proportional hazards regression model will estimate the rPFS treatment hazard ratio with 80% 2-sided confidence intervals (CIs). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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",
From randomization to date of radiographic progression or death due to any cause, whichever occurs first, or censored at the date of last disease assessment. Up to approximately 2 years
Secondary Outcomes (5)
Phase II: rPFS in Patients Without Prior Docetaxel
Up to approximately 2 years after randomization
Phase II: rPFS in Patients With Prior Docetaxel
Up to approximately 2 years after randomization
Phase II: rPFS in Patients With ≤ 20 Bone Lesions
Up to approximately 2 years after randomization
Phase II: rPFS in Patients With > 20 Bone Lesions
Up to approximately 2 years after randomization
Phase II: Overall Survival (OS)
From randomization to the date of death due to any cause, or censored at the date of last follow-up, assessed up to 3.5 years
Other Outcomes (6)
Phase II: rPFS in Patients Without Homologous Recombination Deficiency
Up to approximately 2 years after randomization
Phase II: rPFS in Patients With Homologous Recombination Deficiency
Up to approximately 2 years after randomization
Phase II: Prostate Specific Antigen (PSA) Response
Up to approximately 2 years after randomization
- +3 more other outcomes
Study Arms (4)
Phase II Arm I (radium Ra 223 dichloride, olaparib)
EXPERIMENTALPatients receive radium Ra 223 dichloride IV over 1 minute on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study.
Phase II Arm II (radium Ra 223 dichloride)
EXPERIMENTALPatients receive radium Ra 223 dichloride as in Arm I. Patients with radiographic progression may crossover to Arm I. If patients have already completed all 6 infusions of radium, they will receive monotherapy with olaparib. If they have not yet completed all 6 radium-223 infusion, they will continue radium-223 infusion until completion and receive concurrent treatment with olaparib. Patients also undergo CT or MRI as well as blood sample collection and a tissue biopsy during screening and on study.
Phase I Radium223+Olaparib dose level 1
EXPERIMENTALDose level I: Radium223 plus olaparib 200 mg orally twice daily
Phase I Radium223+Olaparib dose level 2
EXPERIMENTALDose level II: Radium223 plus olaparib 300 mg orally twice daily
Interventions
Given IV
Undergo tissue biopsy
Undergo blood sample collection
Undergo CT
Correlative studies
Undergo MRI
Given PO
Ancillary studies
Eligibility Criteria
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)
- +14 more criteria
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
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Rana Mckay
- Organization
- University of California, San Diego
Study Officials
- PRINCIPAL INVESTIGATOR
Rana R McKay
Yale University Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 20, 2017
First Posted
October 23, 2017
Study Start
February 4, 2019
Primary Completion
March 31, 2025
Study Completion (Estimated)
February 16, 2027
Last Updated
May 5, 2026
Results First Posted
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.