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Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03677076
Recruitment Status : Active, not recruiting
First Posted : September 19, 2018
Last Update Posted : August 11, 2022
Sponsor:
Information provided by (Responsible Party):
Medical University of South Carolina

Tracking Information
First Submitted Date September 18, 2018
First Posted Date September 19, 2018
Last Update Posted Date August 11, 2022
Actual Study Start Date March 4, 2019
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 18, 2018)
Minor allele frequency (MAF) in ctDNA [ Time Frame: 24 months ]
The primary objective is to estimate average change in MAF in one or more clonal SNVs, comparing baseline to on-treatment, and baseline to post-treatment samples
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: September 18, 2018)
  • Changes in MAF of clonal SNV [ Time Frame: 24 months ]
    • Determine if changes from baseline in MAF of clonal SNVs during therapy and post-treatment differ significantly from 0.
  • Change in clonal mutation MAF and change in pain [ Time Frame: 24 months ]
    • Evaluate the association between change from baseline in clonal mutation MAF and change in pain (evaluated by VAS pain score and analgesic usage diary), measured both during therapy and post-treatment.
  • Change in clonal mutation MAF and change in tumor markers [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and change in tumor markers, including prostate specific antigen (PSA), CEA and LDH, measured by standard biochemical assays both during therapy and post-treatment.
  • Change in clonal mutation MAF and markers of bone metabolism [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and markers of bone metabolism including urine N-telopeptide and serum bone-specific alkaline phosphatase, measured by ELISA assays both during therapy and post-treatment.
  • Change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene, measured in plasma/urine by digital PCR Evaluate the association between change in clonal mutation MAF and clinical benefit, (time from the last dose of radium-223 to the initiation of a new systemic therapy, measured at least 60 days after final dose) and change in QOL (measured by FACT-P instrument).
Original Secondary Outcome Measures
 (submitted: September 18, 2018)
  • Changes in MAF of clonal SNV [ Time Frame: 24 months ]
    • Determine if changes from baseline in MAF of clonal SNVs during therapy and post-treatment differ significantly from 0.
  • Change in clonal mutation MAF and change in pain [ Time Frame: 24 months ]
    • Evaluate the association between change from baseline in clonal mutation MAF and change in pain (evaluated by VAS pain score and analgesic usage diary), measured both during therapy and post-treatment.
  • Change in clonal mutation MAF and change in tumor markers [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and change in tumor markers, including PSA, CEA and LDH, measured by standard biochemical assays both during therapy and post-treatment.
  • Change in clonal mutation MAF and markers of bone metabolism [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and markers of bone metabolism including urine N-telopeptide and serum bone-specific alkaline phosphatase, measured by ELISA assays both during therapy and post-treatment.
  • Change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene [ Time Frame: 24 months ]
    • Evaluate the association between change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene, measured in plasma/urine by digital PCR Evaluate the association between change in clonal mutation MAF and clinical benefit, (time from the last dose of radium-223 to the initiation of a new systemic therapy, measured at least 60 days after final dose) and change in QOL (measured by FACT-P instrument).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer
Official Title Clonal Emergence and Regression During Radium-223 Therapy for Metastatic Prostate Cancer
Brief Summary This study is for patients with metastatic prostate cancer receiving radium-223 as their standard of care therapy. The researchers will collect blood and urine samples from patients before, during and after the radium-223 therapy. The researchers will compare these samples to observe how the treatment has affected different cancer markers.
Detailed Description This study proposes to document the presence of clonal emergence and regression during radium-223 therapy for metastatic prostate cancer by serial ctDNA analysis of tumor-associated mutations, using the clinically-available Guardant 360 platform. These data may provide important mechanistic insights into radium-223 therapy by 1) identifying mutations associated with radium-223 resistance or sensitivity, 2) providing new markers of treatment response in an individual, and 3) revealing antitumor effects from radium-223 that are not easily recognized with standard tumor response metrics. Positive finding based on this clinically-available platform will be readily applied by the oncology treatment community.
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population adult males with prostate cancer receiving radium223 treatment
Condition Prostate Cancer
Intervention Other: Ancillary/Correlative
Collection of research blood and urine
Study Groups/Cohorts Ancillary/Correlative
Patients will complete questionnaires and have research blood drawn.
Intervention: Other: Ancillary/Correlative
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 Active, not recruiting
Actual Enrollment
 (submitted: March 30, 2022)
14
Original Estimated Enrollment
 (submitted: September 18, 2018)
30
Estimated Study Completion Date December 31, 2022
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

INCLUSION CRITERIA

  1. Prostate adenocarcinoma by history or medical records.
  2. Two or more bone metastases as demonstrated by imaging studies (technetium bone scan, fluoride PET scan, FDG PET scan, fluciclovine PET scan, CT scan, or MRI scan) or by biopsy.
  3. Patients must be on ADT with a GnRH receptor agonist/antagonist or orchiectomy, with or without an anti-androgen or testosterone synthesis inhibitor. Patients must have a documented castrate level of testosterone (<50ng/dL) and be willing to continue their GnRH agonist/antagonist during the course of radium-223 therapy.
  4. Patients may have had localized external beam radiation to as much as 20% of the skeleton
  5. Adequate hematopoietic, renal, and hepatic function. These parameters include:

    • Hemoglobin ≥ 10gm/dL
    • WBC ≥ 3.0K/mcL
    • ANC ≥ 1.5K/mcL
    • Platelet count ≥ 100K/mcL
    • Creatinine < 1.5 ng/mL
    • Total bilirubin <1.5 ng/mL.
    • Albumin > 25 g/L
  6. Patients should have an elevated, relevant tumor marker such as PSA, CEA, or LDH.
  7. Age ≥18 years old
  8. Life expectancy of at least 24 weeks
  9. Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedures. Subjects must be willing and able to comply with the protocol, including follow-up visits and examinations.
  10. Men of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent until at least 30 days after the last dose of radium-223 treatment or during the course of radium-223 treatment.
  11. Subjects must have had a Guardant 360 ctDNA-based genomic profile performed up to four months prior to the first dose of radium-223, with no new therapy started in the interim. This assay must show at least one single nucleotide variant, either missense or synonymous, or one amplification.
  12. Subjects should continue any previously-started bone-hardening agents (zoledronic acid or denosumab) during radium-223 therapy.
  13. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v 5.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).

EXCLUSION CRITERIA

  1. Initiation of any additional anti-tumor therapy within 2 months of starting radium-223 treatment
  2. Presence of only lytic bone metastases
  3. Prior cytotoxic chemotherapy for metastatic PCa
  4. Prior systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases
  5. Other malignancy requiring systemic therapy within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
  6. Visceral (i.e. liver, lung, brain, adrenal, brain, but not lymph node) metastases as assessed by chest, abdominal, or pelvic computed tomography, or other imaging modality)
  7. Lymphadenopathy exceeding 6 cm in short-axis diameter, or any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis
  8. Imminent spinal cord compression based on clinical findings and/or MRI. Treatment should be completed for spinal cord compression.
  9. Any infection ≥ Grade 2 per NCI-CTCAE version 5.0
  10. Cardiac failure NYHA III or IV
  11. Crohn's disease or ulcerative colitis
  12. Bone marrow dysplasia, myelodysplasia
  13. Fecal incontinence
  14. Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
  15. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  16. Concurrent use of abiraterone or enzalutamide. A 28-day washout period is required for both agents.
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03677076
Other Study ID Numbers 102691
IIR-US-2017-4183 ( Other Identifier: Bayer )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Current Responsible Party Medical University of South Carolina
Original Responsible Party Same as current
Current Study Sponsor Medical University of South Carolina
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: Michael Lilly, MD Medical University of South Carolina
PRS Account Medical University of South Carolina
Verification Date August 2022