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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

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.

Condition or disease Intervention/treatment
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 Procedure: Biospecimen Collection Other: Questionnaire Administration Drug: Radium Ra 223 Dichloride

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.

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Estimated Study Start Date : May 1, 2021
Estimated Primary Completion Date : August 1, 2023
Estimated Study Completion Date : August 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Group/Cohort Intervention/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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Number of radium Ra 223 dichloride [ Time Frame: Up to 6 months ]
  5. Pain assessment [ Time Frame: Up to 1 year ]
    Assessed via Brief Pain Inventory survey

  6. Analgesic usage [ Time Frame: Up to 1 year ]
  7. Quality of life (FACT-P survey) [ Time Frame: Up to 1 year ]
    Assessed via FACT-P quality of life survey

  8. 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.

  9. 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.


Biospecimen Retention:   Samples With DNA
whole blood


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with mCRPC with bone metastases who are undergoing treatment with radium-223
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04489719


Contacts
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Contact: Zoya Bauer (206) 606-7486 zbauer@seattlecca.org

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Zoya Bauer    206-606-7486    zbauer@seattlecca.org   
Principal Investigator: Evan Y. Yu         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Bayer
Investigators
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Principal Investigator: Evan Y. Yu Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: 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 )
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: April 5, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Washington:
Prostate
Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Radium Ra 223 dichloride
Antineoplastic Agents