- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04624256
Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy, GARUDA Trial (GARUDA)
Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy
Study Overview
Status
Conditions
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 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Vince Basehart
- Phone Number: 310-267-8954
- Email: vbasehart@mednet.ucla.edu
Study Contact Backup
- Name: Maria Casado
- Phone Number: 310-794-6913
- Email: mcasado@mednet.ucla.edu
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (radiotherapy, genomic DNA testing)
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.
|
Correlative studies
Ancillary studies
Other Names:
Ancillary studies
Undergo SBRT
Other Names:
Patients and physicians engage in discussion
Other Names:
Undergo conventional hypofractionated radiation therapy
Other Names:
Undergo moderate hypofractionated radiation therapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
5-year cumulative incidence of late grade >= 2 physician-scored genitourinary toxicity
Time Frame: Up to 5 years
|
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 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
5-year biochemical recurrence-free survival
Time Frame: Up to 5 years
|
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).
|
Up to 5 years
|
Rate of acute grade >= 2 genitourinary and gastrointestinal physician-scored toxicity
Time Frame: Up to the first 90 days after radiotherapy
|
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.
|
Up to the first 90 days after radiotherapy
|
Rate of acute grade >= 2 gastrointestinal physician-scored toxicity
Time Frame: Up to the first 90 days after radiotherapy (acute).
|
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.
|
Up to the first 90 days after radiotherapy (acute).
|
5-year cumulative incidence of Late grade >= 2 GU physician-scored toxicity
Time Frame: Up to 5 years
|
Assessed by the CTCAE version 4.03 scale, in patients who test positive or negative for the biomarker.
|
Up to 5 years
|
Proportions of patients who choose to receive radiation treatment
Time Frame: Up to 5 years
|
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.
|
Up to 5 years
|
Change in patient-reported urinary quality of life
Time Frame: Baseline up to 5 years
|
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.
|
Baseline up to 5 years
|
Change in patient-reported bowel quality of life
Time Frame: Baseline up to 5 years
|
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.
|
Baseline up to 5 years
|
Change in patient-reported sexual quality of life outcome
Time Frame: Baseline up to 5 years
|
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.
|
Baseline up to 5 years
|
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
|
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.
|
Baseline up to 5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Amar Kishan, UCLA / Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20-001386
- NCI-2020-07928 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostate Adenocarcinoma
-
Case Comprehensive Cancer CenterTerminatedAdenocarcinoma of Prostate | Adenocarcinoma of the Prostate Stage I | Adenocarcinoma of the Prostate Stage II | Adenocarcinoma of the Prostate Stage IIIUnited States
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States, Canada, Puerto Rico
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)CompletedStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States
-
Dana-Farber Cancer InstituteCompletedProstate Cancer | Adenocarcinoma of the Prostate Stage I | Adenocarcinoma of the Prostate Stage II | Adenocarcinoma of the Prostate Stage IIIUnited States
-
University of California, San FranciscoCompletedProstate Adenocarcinoma | Recurrent Prostate Carcinoma | Stage III Prostate Adenocarcinoma AJCC v7 | Stage I Prostate Adenocarcinoma AJCC v7 | Stage II Prostate Adenocarcinoma AJCC v7United States
-
National Cancer Institute (NCI)Active, not recruitingCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Stage IV Prostate Adenocarcinoma AJCC v7 | Advanced Prostate Adenocarcinoma With Neuroendocrine Differentiation | Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation | Prostate Adenocarcinoma With Neuroendocrine...United States
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnStage II Prostate Adenocarcinoma | Stage I Prostate Adenocarcinoma
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingProstate Adenocarcinoma | Stage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States, Canada, Switzerland
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage III Prostate Adenocarcinoma AJCC v7 | Stage II Prostate Adenocarcinoma AJCC v7 | Stage I Prostate Adenocarcinoma American Joint Committee on Cancer (AJCC) v7United States
-
Andrei IagaruCompletedStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage IV Prostate AdenocarcinomaUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States