Clinical trial NCT04489719: Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Castration-Resistant Prostate Carcinoma
Metastatic Malignant Neoplasm in the Bone
Metastatic Prostate Carcinoma
Stage IVB Prostate Cancer AJCC v8
Keywords: Prostate
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2020-07-28
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with mCRPC with bone metastases who are undergoing treatment with radium-223

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate
timeFrame: Up to 1 year
Secondary outcomes:
measure: Response rate
timeFrame: Up to 1 year
measure: Response rate in those with previous PARP inhibitor therapy
timeFrame: Up to 1 year
measure: Overall survival
timeFrame: Up to 5 years
measure: Number of radium Ra 223 dichloride
timeFrame: Up to 6 months
measure: Pain assessment
timeFrame: Up to 1 year
measure: Analgesic usage
timeFrame: Up to 1 year
measure: Quality of life (FACT-P survey)
timeFrame: Up to 1 year
measure: Incidence of adverse events
timeFrame: Up to 1 year
measure: Response rate
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Evan Y. Yu, MD
role: PRINCIPAL_INVESTIGATOR
References: