Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer

February 12, 2026 updated by: University of Washington

The Impact of DNA Repair Pathway Alterations Identified by Circulating Tumor DNA on Sensitivity to Radium-223 in Bone Metastatic Castration-Resistant Prostate Cancer

This study investigates how well radium-223 works in treating patients with castration-resistant prostate cancer than has spread to the bones (bone metastases). Prostate cancer is the most common cancer in men and the second leading cause of cancer death. Furthermore, many men with notably advanced disease have been found to have abnormalities in DNA repair. The purpose of this research is to study the role of a DNA repair pathway in prostate cancer, specifically in response to administration of radium-223, an FDA-approved drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective treatment in future patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OUTLINE:

Patients receive standard of care radium Ra 223 dichloride given by intravenous (IV) bolus every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months during radium Ra 223 dichloride treatment.

After completion of study, patients are followed up every 3 months for up to 5 years from the date of treatment completion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University
        • Principal Investigator:
          • Ana Kiess, MD
        • Contact:
    • Montana
      • Bozeman, Montana, United States, 59715
        • Active, not recruiting
        • Bozeman Health Deaconess Hospital
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch/University of Washington Cancer Consortium
        • Principal Investigator:
          • Evan Y. Yu, MD
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • Recruiting
        • University of Wisconsin-Madison
        • Principal Investigator:
          • Glenn Liu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with mCRPC with bone metastases who are undergoing treatment with radium-223

Description

Inclusion Criteria:

  • Patient must be >= 18 years of age
  • Patient must have histopathologic diagnosis of prostate cancer
  • Patient must have castration-resistant prostate cancer
  • Patient must have radiographic evidence of bone metastasis
  • Patients must be symptomatic from prostate cancer
  • Patient must have plans to undergo treatment with radium-223
  • Patient must have a PSA level >= 10 ng/mL
  • Patient must have castrate testosterone levels demonstrated within the last 3 months prior to screening
  • Patient must have anticipated survival > 3 months
  • Patient must be willing and able to authorize consent
  • Patient must be willing and able to comply with the protocol, including follow-up visits

Exclusion Criteria:

  • Patient must not have visceral metastasis

  • Patients on regimens of radium-223 in combination with other antineoplastic agents are excluded

    * Bone-targeted only therapy (e.g. denosumab or zoledronic acid) will be allowed

  • Patients who have received prior radium-223
  • Patients who have received prior platinum containing chemotherapy
  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L
  • Hemoglobin (HB) < 9 g/dL
  • Platelets (PLT) < 100 x 10^9/L
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Observational (biospecimen collection)
Patients receive standard of care radium Ra 223 dichloride given by IV bolus every 4 weeks for up to 6 cycles. Patients undergo collection of blood every 1-3 months during radium Ra 223 dichloride treatment.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Radium Ra 223 Dichloride
Given IV
Other Names:
  • Alpharadin
  • BAY 88-8223
  • BAY88-8223
  • Radium 223 Dichloride
  • RADIUM RA-223 DICHLORIDE
  • Radium-223 Dichloride
  • Xofigo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: Up to 1 year
Response will be defined as having one or both of the following: confirmed prostate specific antigen (PSA) decline of >= 30% from baseline AND/OR confirmed alkaline phosphatase (ALP) decline >= 30% from baseline. Response is evaluated throughout the course of treatment until the post-radium-223 end of treatment laboratory studies. Confirmation of response by PSA and/or ALP requires a second consecutive value obtained >= 2 weeks after the first with sustained >= 30% decline. Characterization of response rate to radium-223 in the DRD patient population will be assessed by binomial proportion with Clopper-Pearson exact 2-sided 95% confidence intervals.
Up to 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: Up to 1 year
Comparison of treatment response (outcome/dependent variable) between cases and controls will be assessed using multivariate logistic regression modelling adjusting for secondary variables as appropriate. Risk estimates will include odds ratios with 95% confidence intervals.
Up to 1 year
Response rate in those with previous PARP inhibitor therapy
Time Frame: Up to 1 year
A multivariate logistic model with PARP inhibitor status as a secondary independent variable and a sensitivity analysis excluding those exposed to PARP inhibitors.
Up to 1 year
Overall survival
Time Frame: Up to 5 years
Survival by DRD status will be illustrated using univariate Kaplan-Meier curves. Additionally, Cox-PH model adjusting for age, Eastern Cooperative Oncology Group (ECOG) performance status, Gleason grade score, baseline ALP, PSA, hemoglobin (HB), and lactate dehydrogenase (LDH) will be performed. This analysis may be limited by expected small number of events, thus it may be limited to raw reporting of events by DRD status.
Up to 5 years
Number of radium Ra 223 dichloride
Time Frame: Up to 6 months
Up to 6 months
Pain assessment
Time Frame: Up to 1 year
Assessed via Brief Pain Inventory survey
Up to 1 year
Analgesic usage
Time Frame: Up to 1 year
Up to 1 year
Quality of life (FACT-P survey)
Time Frame: Up to 1 year
Assessed via FACT-P quality of life survey
Up to 1 year
Incidence of adverse events
Time Frame: Up to 1 year
To access risk of adverse events by DRD status, 2 logistic models will be used. The first will classify the dependent variable as an adverse event while the second model will classify the dependent variable as an adverse event < grade 3.
Up to 1 year
Response rate
Time Frame: Up to 1 year
Investigate whether response rates by DRD versus non-DRD patients are modified by germline or somatic alteration status of DNA repair pathways.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Washington

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Evan Y. Yu, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 16, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 23, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 23, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RG1006011
  • NCI-2020-04699 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 10370 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

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