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NCT Number: NCT04147806

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

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.

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Key information

Conditions

Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

50 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467-2490, United States

About this study

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:

  • The dose-fractionation scheme, as per the treatment arm.
  • Acquisition of a set of prostate biopsies at 24 months post treatment
  • Examination of imaging response based on multi-parametric MRI

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

IGRT 45 Gy in 5 fractions of 9 Gy

Radiation

Administration of 9 Gy in five consecutive days, to a total dose of 45 Gy radiation

IGRT 24 Gy single dose

Radiation

Administration of a single dose of 24 Gy in one session

Dexamethasone

Drug

4 mg by mouth on treatment days only

Other names: Dexasone

Tamsulosin

Drug

0.4 mg by mouth daily starting the day of simulation and until 2 weeks post-treatment.

Other names: Flomax Relief

Primary outcomes

  1. Dose-limiting toxicity (DLT)

    Time frame: 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment

    The number of patients with treatment-related DLT will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 criteria. DLT is defined as any Grade 3 genitourinary or gastrointestinal toxicity based on NCI-CTCAE criteria observed within 3 months of completion of protocol radiation therapy. The number of patients exhibiting DLT will be summarized by study arm.

Secondary outcomes

  1. Change in Post-treatment Serum Prostate Specific Antigen (PSA) concentrations

    Time frame: 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment

    Serum blood draws will be collected for determination of PSA concentrations at the specified timepoints during clinical follow-up and analyzed by immunoassay. Change in serum PSA concentrations from baseline will be summarized in units of ng/mL and reported by study arm using basic descriptive statistics.

  2. Post-treatment Prostate Specific Antigen Relapse-free Survival (PSA-RFS)

    Time frame: 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment

    Post-treatment PSA-RFS will be assessed at the specified timepoints during clinical follow-up. PSA-RFS will be defined as the time from the end of radiation therapy to PSA relapse or last follow-up and based on the revised American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Houston definition. The key criterion for biochemical failure as defined by the updated ASTRO definition is a PSA level at or greater than the absolute nadir PSA level plus 2 ng/mL dated at the time of failure. PSA-RFS will be assessed by Kaplan-Meier estimation and summarized by arm at each timepoint.

  3. Pathological Response Rate

    Time frame: 24-36 months following completion of treatment

    Pathological response rate will be evaluated via repeat biopsy samples. For purposes of this study, pathological response rate will be summarized using sample proportions (percentages) and confidence intervals. Pathologic response rates will be divided into 3 categories as per current institutional standard and summarized based on these categories:

    • Prostate adenocarcinoma without typical radiation induced changes;
    • Prostate adenocarcinoma with radiation induced changes; and
    • No evidence of adenocarcinoma.

  4. Quality of life assessment based on International Prostate Symptom Score (IPSS)

    Time frame: 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment

    The IPSS index will be utilized to measure the severity of lower urinary tract symptoms. The IPSS is a 7-item questionnaire designed to assess urinary functioning; specifically, urinary frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, and urgency. Each of the 7 symptom questions is rated on a 6-point Likert scale ranging from 0-5, for an overall possible scoring range of 0-35, with higher scores indicating more difficulty in urinary functioning. Severity thresholds are as follows: 0-7 indicates mild symptoms; 8-19 indicates moderate symptoms; 20-35 indicates severe symptoms. Results will be summarized by arm for each timepoint using basic descriptive statistics.

  5. Quality of life assessment based on International Index of Erectile Function (IIEF)

    Time frame: 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment

    Qualify of life will also be assessed using the IIEF questionnaire. The IIEF is a 15-item questionnaire that assesses five distinct factors (i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction). Each of the 15 questions is rated on 6-point Likert scale ranging from 0-5, for an overall possible scoring range of 0-75. Higher scores are indicative of increased erectile function. Results will be summarized by arm for each timepoint using basic descriptive statistics.

Sponsors and collaborators

Lead sponsor

Albert Einstein College of Medicine

Other

Registry information

Acronym: PROSINT

Important dates

Study start
2016
Primary completion
2026
Study completion
2026
First posted
Nov 1, 2019
Registry last updated
Apr 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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