Castration-Resistant Prostate CarcinomaNCT04489719
Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer
An observational study of Castration-Resistant Prostate Carcinoma and Metastatic Malignant Neoplasm in the Bone, run by University of Washington at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma
- What is being tested?
- Biospecimen Collection, Questionnaire Administration and Radium Ra 223 Dichloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 48 participants
- Where
- 4 sitesUnited States
- Study dates
- 16 Apr 2021to 1 Aug 2030
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Patients with mCRPC with bone metastases who are undergoing treatment with radium-223
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 3 recruiting
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Noura Radwan, 410-614-1570, Nradwan1@jh.edu
Ana Kiess, MD
- Completed
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
- Recruiting
University of Wisconsin-Madison
Madison, Wisconsin, 53705
Glenn Liu, MD
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Jane Romani, 206-606-1909, jromani@fredhutch.org
Evan Y. Yu, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
- Being tested
- Biospecimen Collection, Questionnaire Administration, Radium Ra 223 Dichloride
- Keywords
- Prostate
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Questionnaire AdministrationOther
Ancillary studies
Radium Ra 223 DichlorideDrug
Also called Alpharadin, BAY 88-8223, BAY88-8223, Radium 223 Dichloride
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biospecimen Collection; Other: Questionnaire Administration; Drug: Radium Ra 223 Dichloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 1 year
Secondary outcomes (9)
Response rate
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.
Measured: Up to 1 year
Response rate in those with previous PARP inhibitor therapy
A multivariate logistic model with PARP inhibitor status as a secondary independent variable and a sensitivity analysis excluding those exposed to PARP inhibitors.
Measured: Up to 1 year
Overall survival
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.
Measured: Up to 5 years
Number of radium Ra 223 dichloride
Measured: Up to 6 months
Pain assessment
Assessed via Brief Pain Inventory survey
Measured: Up to 1 year
Analgesic usage
Measured: Up to 1 year
Quality of life (FACT-P survey)
Assessed via FACT-P quality of life survey
Measured: Up to 1 year
Incidence of adverse events
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.
Measured: Up to 1 year
Response rate
Investigate whether response rates by DRD versus non-DRD patients are modified by germline or somatic alteration status of DNA repair pathways.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start16 Apr 2021
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration-Resistant Prostate CarcinomaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Evan Y. Yu, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489719
- Sponsor's protocol ID
- RG1006011
- Other IDs
- NCI-2020-04699, 10370
- Status last verified
- Aug 2026
- First submitted
- 23 Jul 2020
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No