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.

Condition

Eligibility

Eligible Ages
Over 50 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
IGRT 45 Gy in 5 fractions of 9 Gy
Hypofractionated IGRT at a prescription dose of 45 Gy in 5 fractions of 9 Gy delivered in five consecutive days
  • Radiation: IGRT 45 Gy in 5 fractions of 9 Gy
    Administration of 9 Gy in five consecutive days, to a total dose of 45 Gy radiation
  • Radiation: IGRT 24 Gy single dose
    Administration of a single dose of 24 Gy in one session
  • Drug: Dexamethasone
    4 mg by mouth on treatment days only
  • Drug: Tamsulosin
    0.4 mg by mouth daily starting the day of simulation and until 2 weeks post-treatment.
Experimental
IGRT 24 Gy single dose
single fraction IGRT at a prescription dose of 24 Gy
  • Radiation: IGRT 45 Gy in 5 fractions of 9 Gy
    Administration of 9 Gy in five consecutive days, to a total dose of 45 Gy radiation
  • Radiation: IGRT 24 Gy single dose
    Administration of a single dose of 24 Gy in one session
  • Drug: Dexamethasone
    4 mg by mouth on treatment days only
  • Drug: Tamsulosin
    0.4 mg by mouth daily starting the day of simulation and until 2 weeks post-treatment.

Recruiting Locations

Montefiore Medical Center - Moses Campus
Bronx, New York 10467-2490
Contact:
Madhur K. Garg
718-920-4361
aecc@aecom.yu.edu

More Details

Status
Recruiting
Sponsor
Albert Einstein College of Medicine

Study Contact

Sarah Yukelis
718-920-5636
syukelis@montefiore.org

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.