Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
Conditions
Keywords
Prostate
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.
Interventions
PROCEDUREBiospecimen Collection
Undergo collection of blood samples
OTHERQuestionnaire Administration
Ancillary studies
Given IV
Sponsors
University of Washington
Bayer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | Up to 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | Up to 1 year | 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. |
| Response rate in those with previous PARP inhibitor therapy | Up to 1 year | A multivariate logistic model with PARP inhibitor status as a secondary independent variable and a sensitivity analysis excluding those exposed to PARP inhibitors. |
| Overall survival | Up to 5 years | 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. |
| Number of radium Ra 223 dichloride | Up to 6 months | — |
| Pain assessment | Up to 1 year | Assessed via Brief Pain Inventory survey |
| Analgesic usage | Up to 1 year | — |
| Quality of life (FACT-P survey) | Up to 1 year | Assessed via FACT-P quality of life survey |
| Incidence of adverse events | Up to 1 year | 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. |
Countries
United States
Contacts
CONTACTJane Romani
PRINCIPAL_INVESTIGATOREvan Y. Yu, MD
Fred Hutch/University of Washington Cancer Consortium
Outcome results
None listed