Clinical Trials /

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

NCT03677076

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 102691
  • SECONDARY ID: IIR-US-2017-4183
  • NCT ID: NCT03677076

Conditions

  • Prostate Cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Ancillary/CorrelativeOtherPatients will complete questionnaires and have research blood drawn.

    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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Minor allele frequency (MAF) in ctDNA
    Time Frame:24 months
    Safety Issue:
    Description: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

    Secondary Outcome Measures

    Measure:Changes in MAF of clonal SNV
    Time Frame:24 months
    Safety Issue:
    Description:• Determine if changes from baseline in MAF of clonal SNVs during therapy and post-treatment differ significantly from 0.
    Measure:Change in clonal mutation MAF and change in pain
    Time Frame:24 months
    Safety Issue:
    Description:• 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.
    Measure:Change in clonal mutation MAF and change in tumor markers
    Time Frame:24 months
    Safety Issue:
    Description:• 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.
    Measure:Change in clonal mutation MAF and markers of bone metabolism
    Time Frame:24 months
    Safety Issue:
    Description:• 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.
    Measure:Change in clonal mutation MAF and presence of the TMPRSS2-ERG fusion gene
    Time Frame:24 months
    Safety Issue:
    Description:• 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).

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Medical University of South Carolina

    Last Updated

    April 24, 2019