Description:
The present study evaluates clinical outcomes and treatment-related toxicity following
definitive ultra-high dose external beam radiotherapy delivered with two different regimens
in patients with intermediate-risk adenocarcinoma of the prostate. Modern computer-driven
technology enables the implementation of ultra-high hypofractionated Image-Guided
Radiotherapy (IGRT) safely.
Prostate cancer patients classified according to the current National Comprehensive Cancer
Network (NCCN) guidelines as intermediate risk (biopsy Gleason score of 7 and/or Prostate
Specific Antigen (PSA) level >10 and ≤20 ng/mL and/or Stage T1, T2a, T2b or T2c) are eligible
for this study.
Patients will undergo IGRT with volumetric intensity-modulated arc radiotherapy (VMAT) with
state-of-the-art treatment-planning and quality assurance procedures. Emphasis is placed on
normal tissue sparing and delivery accuracy via the use of devices that ensure stability and
beam location reproducibility. A rectal balloon with air filling will be used for prostate
target immobilization and anatomical reproducibility, while a urethral catheter loaded with
beacon transponders will be used to ensure set-up reproducibility and online target tracking.
Previously untreated patients with intermediate-risk prostate cancer will be prospectively
randomized to receive either 45 Gy in five fractions of 9 Gy each vs. 24 Gy in a single-dose.
Patients will be followed at one month post-treatment and every 3 months for up to 12 months
(+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will
focus on urinary, rectal and sexual functions and will be assessed through validated
questionnaires. Serum PSA values will be regularly acquired during follow-up. A
multiparametric MRI will be performed at baseline, 6, 12 and 24 months following
intervention. Additionally, a post-treatment diffusion-weighted MRI (DW-MRI) will be
performed within 15 minutes of the first treatment, to measure early physiologic changes,
such as perfusion and ischemia, that may correlate with clinically relevant end-points.
Post-treatment prostate needle biopsies will be obtained at 24 months to evaluate pathologic
response to therapy. The study will be continuously monitored for a minimum of 5 years. In
the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment
arms, the study will be terminated according to the stopping rule >3/first 15 patients.
Title
- Brief Title: A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer
- Official Title: A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
2016-6545
- NCT ID:
NCT04147806
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Dexamethasone | Dexasone | IGRT 24 Gy single dose |
| Tamsulosin | Flomax Relief | IGRT 24 Gy single dose |
Purpose
The present study evaluates clinical outcomes and treatment-related toxicity following
definitive ultra-high dose external beam radiotherapy delivered with two different regimens
in patients with intermediate-risk adenocarcinoma of the prostate. Modern computer-driven
technology enables the implementation of ultra-high hypofractionated Image-Guided
Radiotherapy (IGRT) safely.
Prostate cancer patients classified according to the current National Comprehensive Cancer
Network (NCCN) guidelines as intermediate risk (biopsy Gleason score of 7 and/or Prostate
Specific Antigen (PSA) level >10 and ≤20 ng/mL and/or Stage T1, T2a, T2b or T2c) are eligible
for this study.
Patients will undergo IGRT with volumetric intensity-modulated arc radiotherapy (VMAT) with
state-of-the-art treatment-planning and quality assurance procedures. Emphasis is placed on
normal tissue sparing and delivery accuracy via the use of devices that ensure stability and
beam location reproducibility. A rectal balloon with air filling will be used for prostate
target immobilization and anatomical reproducibility, while a urethral catheter loaded with
beacon transponders will be used to ensure set-up reproducibility and online target tracking.
Previously untreated patients with intermediate-risk prostate cancer will be prospectively
randomized to receive either 45 Gy in five fractions of 9 Gy each vs. 24 Gy in a single-dose.
Patients will be followed at one month post-treatment and every 3 months for up to 12 months
(+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will
focus on urinary, rectal and sexual functions and will be assessed through validated
questionnaires. Serum PSA values will be regularly acquired during follow-up. A
multiparametric MRI will be performed at baseline, 6, 12 and 24 months following
intervention. Additionally, a post-treatment diffusion-weighted MRI (DW-MRI) will be
performed within 15 minutes of the first treatment, to measure early physiologic changes,
such as perfusion and ischemia, that may correlate with clinically relevant end-points.
Post-treatment prostate needle biopsies will be obtained at 24 months to evaluate pathologic
response to therapy. The study will be continuously monitored for a minimum of 5 years. In
the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment
arms, the study will be terminated according to the stopping rule >3/first 15 patients.
Detailed Description
This is open label feasibility study where patients enrolled in the study will undergo
image-guided, intensity-modulated radiotherapy using the same equipment, techniques, and
treatment-planning procedures as currently practiced at CCU. Eligible patients will receive
either 45 Gy in 5 sessions each of 9 Gy delivered in one week (arm A) or 24 Gy in 1 session
(arm B) to assess the dose limiting toxicities in the two groups. Patients will be randomized
to arm A or arm B.
Dose limiting toxicity (DLT) is defined as any Grade 3 urinary or rectal toxicity, based on
NCI CTCAE v4.0, observed within 3 months of completion of protocol radiation. If, at any
point in the conduct of the trial, DLTs are observed in three patients in a study arm,
accrual to that arm will be terminated.
There are three aspects of this study that will be different from the currently used standard
treatment for definitive external beam treatment of prostate cancer:
1. The dose-fractionation scheme, as per the treatment arm.
2. Acquisition of a set of prostate biopsies at 24 months post treatment
3. Examination of imaging response based on multi-parametric MRI
Trial Arms
| Name | Type | Description | Interventions |
|---|
| IGRT 45 Gy in 5 fractions of 9 Gy | Active Comparator | Hypofractionated IGRT at a prescription dose of 45 Gy in 5 fractions of 9 Gy delivered in five consecutive days | |
| IGRT 24 Gy single dose | Experimental | single fraction IGRT at a prescription dose of 24 Gy | |
Eligibility Criteria
Inclusion Criteria:
- Signed study specific informed consent form;
- Histologic confirmation of adenocarcinoma of the prostate by biopsy;
- PSA ≤ 20 ng/mL;
- Gleason score 7;
- Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b
or T2c;
- No direct evidence of regional or distant metastases after appropriate staging
studies;
- Age ≥ 50;
- Performance Status 0-2;
- Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
- CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;
Exclusion Criteria:
- Positive lymph-nodes or metastatic disease from prostate cancer on imaging studies
- Prior invasive malignancy unless disease-free for a minimum of 5 years
- Tumour Clinical stage T3 or T4 on MRI
- PSA > 20 ng/mL
- Gleason score > 7
- Previous pelvic radiotherapy
- Previous surgery for prostate cancer
- Previous transurethral resection of the prostate (TURP)
- History of Crohn's Disease or Ulcerative Colitis
- Previous significant urinary obstructive symptoms
- Significant psychiatric illness
- Ultrasound or CT estimate of prostate volume > 100 grams
- Severe, active co-morbidity
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 50 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of patients with treatment-related adverse events as assessed by Common Toxicity Criteria for Adverse Effects v4.0 |
| Time Frame: | Participants should be followed continuously, for the duration of 5 years |
| Safety Issue: | |
| Description: | Comparison of treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0 over a 5 year time frame |
Secondary Outcome Measures
| Measure: | Biochemical outcome based on Prostate Specific Antigen (PSA) assessment |
| Time Frame: | Participants should be followed continuously for the duration of 5 years |
| Safety Issue: | |
| Description: | PSA assessment will be done |
| Measure: | Quality of life assessment based on International Prostate Symptom Score (IPSS) |
| Time Frame: | Participants should be followed continuously for the duration of 5 years |
| Safety Issue: | |
| Description: | The International Prostate Symptom Score (IPSS) can be utilized to measure the severity of lower urinary tract symptoms.The IPSS is made up of 7 questions related to voiding symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms and 20 to 35 indicates severe symptoms. |
| Measure: | Pathological response based on biopsy at 24 months post-treatment |
| Time Frame: | Participants should be followed continuously for the duration of 5 years |
| Safety Issue: | |
| Description: | Pathology will be evaluated |
| Measure: | Quality of life assessment based on International Index of Erectile Function (IIEF) |
| Time Frame: | Participants should be followed continuously for the duration of 5 years |
| Safety Issue: | |
| Description: | Quality of life survey |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Albert Einstein College of Medicine |
Last Updated
August 25, 2021
