Clinical Trials /

Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy, GARUDA Trial

NCT04624256

Description:

This trial studies the changes in long-term physician-scored genitourinary toxicity achieved in prostate cancer patients eligible for stereotactic radiation therapy when both patients and physicians have access to convincing but non-validated germline signature that can characterize patients as having a low or high risk of developing toxicity after radiation therapy. The information learned from this study may guide patients' and physicians' decisions on radiotherapy fractionation.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Germine DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy, GARUDA Trial
  • Official Title: Germine DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy (GARUDA)

Clinical Trial IDs

  • ORG STUDY ID: 20-001386
  • SECONDARY ID: NCI-2020-07928
  • SECONDARY ID: 20-001386
  • NCT ID: NCT04624256

Conditions

  • Prostate Adenocarcinoma
  • Stage I Prostate Cancer American Joint Committee on Cancer (AJCC) v8
  • Stage II Prostate Cancer AJCC v8
  • Stage IIA Prostate Cancer AJCC v8
  • Stage IIB Prostate Cancer AJCC v8
  • Stage IIC Prostate Cancer AJCC v8

Purpose

This trial studies the changes in long-term physician-scored genitourinary toxicity achieved in prostate cancer patients eligible for stereotactic radiation therapy when both patients and physicians have access to convincing but non-validated germline signature that can characterize patients as having a low or high risk of developing toxicity after radiation therapy. The information learned from this study may guide patients' and physicians' decisions on radiotherapy fractionation.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the impact on the 5-year cumulative incidence of late grade >= 2
      genitourinary (GU) physician-scored toxicity, as assessed by the Common Terminology Criteria
      for Adverse Events (CTCAE) version 4.03 scale, caused by presenting both the physicians and
      patients with the results of a non-prospectively validated biomarker panel that dichotomizes
      any given patient into having a high versus a low risk of late grade >= 2 GU physician-scored
      toxicity following stereotactic body radiotherapy (SBRT).

      SECONDARY OBJECTIVES:

      I. To determine the late grade >= 2 genitourinary (GU) physician-scored toxicity, as assessed
      by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale, in patients
      who test positive for the biomarker.

      II. To determine the late grade >= 2 genitourinary (GU) physician-scored toxicity, as
      assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale, in
      patients who test negative for the biomarker.

      III. To observe the proportions of patients who choose to receive conventionally fractionated
      radiotherapy, moderately hypofractionated radiotherapy, and SBRT, based on being positive or
      negative for the biomarker thought to predict for late grade >= 2 GU toxicity.

      IV. To determine the 5-year cumulative incidence of late grade >= 2 gastrointestinal (GI)
      physician-reported toxicity, as assessed by the CTCAE version 4.03 scale, following the same
      intervention as for the primary objective.

      V. To determine the incidence of acute grade >= 2 GU and GI toxicity as assessed by the CTCAE
      version 4.03 scale, following the same intervention as for the primary objective.

      VI. To quantify the temporal changes in patient-reported quality of life (QOL) outcomes, as
      assessed by the Expanded Prostate Cancer Index-26 (EPIC-26), International Prostate Symptom
      Scores (IPSS), and Sexual Health Inventory for Men (SHIM) QOL indices, following the same
      intervention as for the primary objective.

      OUTLINE:

      Patients undergo SBRT per standard of care, then undergo collection of cheek swab and blood
      samples for the analysis of germline biomarkers. Afterwards, patients and their physicians
      engage in discussion about which form of radiotherapy to proceed with. Based on the decision,
      patients predicted to be at low risk of toxicity with SBRT continue to receive SBRT over 14
      days while patients predicted to be at high risk of toxicity with SBRT will be counseled to
      undergo either conventionally fractionated radiotherapy over 63-70 days, moderate
      hypofractionated radiotherapy over 28-35 days, or may opt to still receive SBRT over 14 days
      per standard of care.

      After completion of radiotherapy treatment, patients are followed up at 1 ,3, 6, 9, 12, 18,
      and 24 months, and then every 6 months for 4 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (radiotherapy, genomic DNA testing)ExperimentalPatients undergo SBRT per standard of care, then undergo collection of cheek swab and blood samples for the analysis of germline biomarkers. Afterwards, patients and their physicians engage in discussion about which form of radiotherapy to proceed with. Based on the decision, patients predicted to be at low risk of toxicity with SBRT continue to receive SBRT over 14 days while patients predicted to be at high risk of toxicity with SBRT will be counseled to undergo either conventionally fractionated radiotherapy over 63-70 days, moderate hypofractionated radiotherapy over 28-35 days, or may opt to still receive SBRT over 14 days per standard of care.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed, clinical localized adenocarcinoma of the prostate
    
              -  No evidence of disease beyond the prostate and/or seminal vesicles (i.e., no
                 suspicious pelvic lymph nodes or presence of metastatic disease outside the pelvis)
    
              -  Staging workup as recommended by the National Comprehensive Cancer Network (NCCN) on
                 the basis of risk grouping:
    
                   -  Low risk: No staging workup required
    
                   -  Favorable intermediate-risk: computed tomography (CT) abdomen/pelvis only if
                      Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicts > 10%
                      probability of lymph node involvement (note: CT simulation scan will count as a
                      CT abdomen/pelvis)
    
                   -  Unfavorable intermediate-risk: technetium bone scan, CT abdomen/pelvis if MSKCC
                      nomogram predicts > 10% probability of lymph node involvement (note: CT
                      simulation scan will count as a CT abdomen/pelvis)
    
                   -  High-risk: technetium bone scan, CT abdomen/pelvis if MSKCC nomogram predicts >
                      10% probability of lymph node involvement (note: CT simulation scan will count as
                      a CT abdomen/pelvis) =
    
                   -  Advanced imaging studies (i.e. prostate specific membrane antigen [PSMA] positron
                      emission tomography [PET] and Axumin scan) can supplant a bone scan if performed
                      first
    
              -  Ability to understand, and willingness to sign, the written informed consent
    
            Exclusion Criteria:
    
              -  Patients with neuroendocrine or small cell carcinoma of the prostate
    
              -  Patients with any evidence of distant metastases. Note, evidence of lymphadenopathy
                 below the level of the renal arteries can be deemed loco regional per the discretion
                 of the investigator
    
              -  Prior whole-gland cryosurgery, high-intensity focused ultrasound (HIFU) or
                 brachytherapy of the prostate
    
              -  Prior pelvic radiotherapy
    
              -  History of Crohn's disease, ulcerative colitis, or ataxia telangiectasia
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:5-year cumulative incidence of late grade >= 2 physician-scored genitourinary toxicity
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale, stratified by positive or negative status for the biomarker thought to predict for late grade >= 2 genitourinary (GU) toxicity.

    Secondary Outcome Measures

    Measure:5-year biochemical recurrence-free survival
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be estimated by the Kaplan-Meier method, with biochemical recurrence (BCR) defined as serum prostate specific antigen (PSA) levels that are 2 ng/mL higher than the nadir PSA achieved after magnetic resonance imaging-guided stereotactic body radiation therapy (SBRT).
    Measure:Rate of acute grade >= 2 genitourinary and gastrointestinal physician-scored toxicity
    Time Frame:Up to the first 90 days after radiotherapy
    Safety Issue:
    Description:Assessed by the CTCAE version 4.03 scale, based on being positive or negative for the biomarker thought to predict for late grade >= 2 GU toxicity. The timeframe will be restricted to the first 90 days after radiotherapy.
    Measure:Rate of acute grade >= 2 gastrointestinal physician-scored toxicity
    Time Frame:Up to the first 90 days after radiotherapy (acute).
    Safety Issue:
    Description:Assessed by the CTCAE version 4.03 scale, based on being positive or negative for the biomarker thought to predict for late grade >= 2 GU toxicity.
    Measure:5-year cumulative incidence of Late grade >= 2 GU physician-scored toxicity
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Assessed by the CTCAE version 4.03 scale, in patients who test positive or negative for the biomarker.
    Measure:Proportions of patients who choose to receive radiation treatment
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will analyze the proportions of patients who choose to receive conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and SBRT, based on being positive or negative for the biomarker thought to predict for late grade >= 2 GU toxicity.
    Measure:Change in patient-reported urinary quality of life
    Time Frame:Baseline up to 5 years
    Safety Issue:
    Description:Will be obtained depending on the instrument used. For the Expanded Prostate Cancer Index-26 instrument, these will be represented by changes from baseline in the urinary symptom domain. The scores will range from 0-100, with a higher number indicating a better quality of life. Changes will be analyzed with respect to whether they represent minimally important differences, based on approved thresholds in the literature.
    Measure:Change in patient-reported bowel quality of life
    Time Frame:Baseline up to 5 years
    Safety Issue:
    Description:Will be obtained depending on the instrument used. For the Expanded Prostate Cancer Index-26 instrument, these will be represented by changes from baseline in the bowel domain. The scores will range from 0-100, with a higher number indicating a better quality of life. Changes will be analyzed with respect to whether they represent minimally important differences.
    Measure:Change in patient-reported sexual quality of life outcome
    Time Frame:Baseline up to 5 years
    Safety Issue:
    Description:will be assessed by the International Prostate Symptom Scores (I-PSS) instrument by five years. Scoring is from 1 - 35, a higher number is worse outcome.
    Measure:Change in patient-reported sexual quality of life by the Sexual Health Inventory for Men instrument by five years
    Time Frame:Baseline up to 5 years
    Safety Issue:
    Description:Will be represented by changes from baseline in the urinary incontinence and urinary obstruction domains on the Sexual Health Inventory for Men instrument (SHIM). coring from 1-25, higher number is better outcome.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Jonsson Comprehensive Cancer Center

    Last Updated

    November 5, 2020