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

NCT04147806 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 2016-6545
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with treatment-related adverse events as assessed by Common Toxicity Criteria for Adverse Effects v4.0

  Comparison of treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0 over a 5 year time frame

  Participants should be followed continuously, for the duration of 5 years

Secondary Outcomes (4)

• Biochemical outcome based on Prostate Specific Antigen (PSA) assessment

  Participants should be followed continuously for the duration of 5 years

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

  Participants should be followed continuously for the duration of 5 years

• Pathological response based on biopsy at 24 months post-treatment

  Participants should be followed continuously for the duration of 5 years

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

  Participants should be followed continuously for the duration of 5 years

Study Arms (2)

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

Radiation: IGRT 45 Gy in 5 fractions of 9 Gy; Radiation: IGRT 24 Gy single dose; Drug: Dexamethasone; Drug: Tamsulosin

IGRT 24 Gy single dose

EXPERIMENTAL

single fraction IGRT at a prescription dose of 24 Gy

Radiation: IGRT 45 Gy in 5 fractions of 9 Gy; Radiation: IGRT 24 Gy single dose; Drug: Dexamethasone; Drug: Tamsulosin

Interventions

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; IGRT 45 Gy in 5 fractions of 9 Gy

IGRT 24 Gy single dose RADIATION

Administration of a single dose of 24 Gy in one session

IGRT 24 Gy single dose; IGRT 45 Gy in 5 fractions of 9 Gy

Dexamethasone DRUG

4 mg by mouth on treatment days only

Also known as: Dexasone

IGRT 24 Gy single dose; IGRT 45 Gy in 5 fractions of 9 Gy

Tamsulosin DRUG

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

Also known as: Flomax Relief

IGRT 24 Gy single dose; IGRT 45 Gy in 5 fractions of 9 Gy

Eligibility Criteria

• Age: 50 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead

Study Sites (1)

Montefiore Medical Center - Moses Campus

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

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dexamethasone; Tamsulosin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Madhur Garg, MD

  Associate Clinical Director

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: November 1, 2019
• Study Start: August 1, 2016
• Primary Completion (Estimated): July 13, 2026
• Study Completion (Estimated): July 13, 2026
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)