RecruitingObservational

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

NCT ID: NCT04489719Sponsor: University of WashingtonLast updated: 2026-02-17

Summary

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.

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.

Arms & interventions

ProcedureBiospecimen Collection
Undergo collection of blood samples
OtherQuestionnaire Administration
Ancillary studies
DrugRadium Ra 223 Dichloride
Given IV

Outcome measures

Primary

Response rate
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.
Time frame: Up to 1 year

Secondary

Response rate
Time frame: Up to 1 year
Response rate in those with previous PARP inhibitor therapy
Time frame: Up to 1 year
Overall survival
Time frame: Up to 5 years
Number of radium Ra 223 dichloride
Time frame: Up to 6 months
Pain assessment
Time frame: Up to 1 year
Analgesic usage
Time frame: Up to 1 year
Quality of life (FACT-P survey)
Time frame: Up to 1 year
Incidence of adverse events
Time frame: Up to 1 year
Response rate
Time frame: Up to 1 year

Eligibility criteria

Sex: MaleAge: 18 Years and olderHealthy volunteers: No

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 locations (4)

Johns Hopkins University

Baltimore, Maryland, 21287

Recruiting

Noura Radwan · Contact

410-614-1570 Nradwan1@jh.edu

Ana Kiess, MD · Principal Investigator

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715

Active Not Recruiting

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

Recruiting

Jane Romani · Contact

206-606-1909 jromani@fredhutch.org

Evan Y. Yu, MD · Principal Investigator

University of Wisconsin-Madison

Madison, Wisconsin, 53705

Recruiting

Glenn Liu, MD · Principal Investigator