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

Description
This phase II 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.

Objective
Determine the response rate of bone mCRPC patients with DNA repair deficiency (DRD) to treatment with radium-223. Response will be defined as having one or both of the following:
-Confirmed PSA decline of >30% from baseline
AND/OR
-Confirmed alkaline phosphatase (ALP) decline of >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.

Treatment 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
Undergo collection of blood samples

Other: Questionnaire Administration
Ancillary studies

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

Key Eligibility Inclusion Criteria:

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

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

Applicable Disease Sites
Prostate

Participating Institutions
UW Health University Hospital