NCT04624256 - Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy, GARUDA Trial

PRIMARY OBJECTIVE: I. To determine the impact on the 2-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. To determine the 2- and 5-year cumulative incidences 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. IV. 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. V. 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. VI. To determine the 5-year cumulative incidence of late grade ≥2 GU physician-reported toxicity, as assessed by the CTCAE version 4.03 scale. OUTLINE: Patients planning to undergo SBRT per standard of care 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.