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.
Recruiting
N/A
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
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 |
| 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. |
| 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. |
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Jonsson Comprehensive Cancer Center |
November 16, 2020
