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

NCT04489719 | Recruiting

• 3 other identifiers: RG1006011NCI-2020-0469910370
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8

Keywords

Prostate

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 1 year

Secondary Outcomes (9)

• Response rate

  Up to 1 year

• Response rate in those with previous PARP inhibitor therapy

  Up to 1 year

• Overall survival

  Up to 5 years

• Number of radium Ra 223 dichloride

  Up to 6 months

• Pain assessment

  Up to 1 year

Study Arms (1)

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.

Procedure: Biospecimen Collection; Other: Questionnaire Administration; Drug: Radium Ra 223 Dichloride

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Observational (biospecimen collection)

Questionnaire Administration OTHER

Ancillary studies

Observational (biospecimen collection)

Radium Ra 223 Dichloride DRUG

Given IV

Also known as: Alpharadin, BAY 88-8223, BAY88-8223, Radium 223 Dichloride, RADIUM RA-223 DICHLORIDE, Radium-223 Dichloride, Xofigo

Observational (biospecimen collection)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Bayer: collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States

ACTIVE NOT RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

University of Wisconsin-Madison

Madison, Wisconsin, 53705, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

whole blood

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Specimen Handling; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Evan Y. Yu, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jane Romani

CONTACT

206-606-1909; jromani@fredhutch.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 28, 2020
• Study Start: April 16, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2029
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)