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

NCT04624256 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: 20-001386NCI-2020-07928
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (1)

• 2-year cumulative incidence of late grade >= 2 physician-scored genitourinary toxicity

  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.

  Up to 2 years

Secondary Outcomes (9)

• Late grade ≥2 genitourinary (GU) physician-scored toxicity in patients who test positive for the biomarker

  Up to 5 years

• Late grade ≥2 genitourinary (GU) physician-scored toxicity in patients who test negative for the biomarker

  Up to the first 90 days after radiotherapy

• 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.

  Up to the first 90 days after radiotherapy (acute).

• 2- and 5-year cumulative incidences of late grade ≥2 GI physician-reported toxicity, based on being positive or negative for the biomarker thought to predict for late grade ≥2 GU toxicity.

  Up to 5 years

• Acute grade ≥2 GU and GI toxicity based on being positive or negative for the biomarker thought to predict for late grade ≥2 GU toxicity.

  Up to 90 days

Study Arms (1)

Treatment (radiotherapy, genomic DNA testing)

EXPERIMENTAL

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.

Procedure: Discussion; Radiation: Hypofractionated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy

Interventions

Discussion PROCEDURE

Patients and physicians engage in discussion

Also known as: Discuss

Treatment (radiotherapy, genomic DNA testing)

Hypofractionated Radiation Therapy RADIATION

Undergo conventional hypofractionated radiation therapy

Also known as: Hypofractionated Radiotherapy, hypofractionation

Treatment (radiotherapy, genomic DNA testing)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (radiotherapy, genomic DNA testing)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (radiotherapy, genomic DNA testing)

Questionnaire Administration OTHER

Ancillary studies

Treatment (radiotherapy, genomic DNA testing)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (radiotherapy, genomic DNA testing)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• MiraDX: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiation Dose Hypofractionation; Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Amar Kishan

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 10, 2020
• Study Start: November 10, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 13, 2026

Record last verified: 2025-05

Locations

US (1)