Clinical Trials /

A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer

NCT04147806

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Prostate Cancer

Interventions

DrugSynonymsArms
DexamethasoneIGRT 45 Gy in 5 fractions of 9 Gy
TamsulosinIGRT 45 Gy in 5 fractions of 9 Gy

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.

Trial Arms

NameTypeDescriptionInterventions
IGRT 45 Gy in 5 fractions of 9 GyActive ComparatorHypofractionated IGRT at a prescription dose of 45 Gy in 5 fractions of 9 Gy delivered in five consecutive days
  • Dexamethasone
  • Tamsulosin
IGRT 24 Gy single doseExperimentalsingle fraction IGRT at a prescription dose of 24 Gy
  • Dexamethasone
  • Tamsulosin

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:
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:
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:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Albert Einstein College of Medicine

Last Updated

October 31, 2019