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

Metastatic Prostate Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04489719
• Other study ID #: RG1006011
• Secondary ID: NCI-2020-0469910
• Status: Recruiting
• Start date: April 16, 2021
• Est. completion date: August 1, 2028

Study information

• Verified date: May 2024
• Source: University of Washington
• Contact: Patrick Panlasigui
• Phone: 206-606-7486
• Email: ppanlas2[@]fredhutch.org
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: August 1, 2028
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Malignant Neoplasm in the Bone
• Metastatic Prostate Carcinoma
• Neoplasms
• Prostatic Neoplasms
• Stage IV Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8
• Stage IVB Prostate Cancer AJCC v8

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood samples

Other:
• Questionnaire Administration
Ancillary studies

Drug:
• Radium Ra 223 Dichloride
Given IV

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 1 year
Secondary	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.	Up to 1 year
Secondary	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.	Up to 1 year
Secondary	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.	Up to 5 years
Secondary	Number of radium Ra 223 dichloride		Up to 6 months
Secondary	Pain assessment	Assessed via Brief Pain Inventory survey	Up to 1 year
Secondary	Analgesic usage		Up to 1 year
Secondary	Quality of life (FACT-P survey)	Assessed via FACT-P quality of life survey	Up to 1 year
Secondary	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.	Up to 1 year
Secondary	Response rate	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