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

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ClinicalTrials.gov Identifier: NCT04489719
Recruitment Status : Recruiting
First Posted : July 28, 2020
Last Update Posted : April 5, 2021
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Bayer
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date July 23, 2020
First Posted Date July 28, 2020
Last Update Posted Date April 5, 2021
Estimated Study Start Date May 1, 2021
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 23, 2020)
Response rate [ Time Frame: 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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 23, 2020)
  • Response rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 6 months ]
  • Pain assessment [ Time Frame: Up to 1 year ]
    Assessed via Brief Pain Inventory survey
  • Analgesic usage [ Time Frame: Up to 1 year ]
  • Quality of life (FACT-P survey) [ Time Frame: Up to 1 year ]
    Assessed via FACT-P quality of life survey
  • Incidence of adverse events [ Time Frame: 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.
  • Response rate [ Time Frame: Up to 1 year ]
    Investigate whether response rates by DRD versus non-DRD patients are modified by germline or somatic alteration status of DNA repair pathways.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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
Brief Summary 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.
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood
Sampling Method Non-Probability Sample
Study Population Patients with mCRPC with bone metastases who are undergoing treatment with radium-223
Condition
  • Castration-Resistant Prostate Carcinoma
  • Metastatic Malignant Neoplasm in the Bone
  • Metastatic Prostate Carcinoma
  • 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
    Other Names:
    • Alpharadin
    • BAY 88-8223
    • BAY88-8223
    • Radium 223 Dichloride
    • RADIUM RA-223 DICHLORIDE
    • Radium-223 Dichloride
    • Xofigo
Study Groups/Cohorts 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.
Interventions:
  • Procedure: Biospecimen Collection
  • Other: Questionnaire Administration
  • Drug: Radium Ra 223 Dichloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 23, 2020)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 1, 2027
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patient must have histopathologic diagnosis of prostate cancer
  • Patient must meet Food and Drug Administration (FDA) approved criteria (e.g., mCRPC, radiographic evidence of bone metastasis, symptomatic from prostate cancer) for receipt of radium-223 with plans to undergo treatment with such
  • Patient must have a prostate specific antigen (PSA) level > 20 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
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Zoya Bauer (206) 606-7486 zbauer@seattlecca.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04489719
Other Study ID Numbers RG1006011
NCI-2020-04699 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10370 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Washington
Study Sponsor University of Washington
Collaborators
  • National Cancer Institute (NCI)
  • Bayer
Investigators
Principal Investigator: Evan Y. Yu Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date January 2021