Dose Escalation Study of Preoperative SBRT for High Risk Prostate Cancer

A Phase I Dose Escalation Study of Preoperative Stereotactic Body Radiation Therapy (SBRT) for High Risk Prostate Cancer

The purpose of this study is to compare the effects, good and/or bad, of different doses of SBRT given before prostatectomy. Depending when participants enter the study, they will be treated with either 5 or 6 gray (Gy) per day of radiation. A Gy is a measure of radiation dose. The standard dose is 10Gy per day when SBRT is the only treatment to the prostate and no surgery is planned. The researchers want to see which dose of radiation will work best with the least amount of side effects. About 4-6 weeks after SBRT, participants will have a prostatectomy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Prostatectomy; Other: Quality of Life Questionnaires

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically-proven prostate adenocarcinoma.
• Clinical stage ≤T3a based on digital rectal exam and/or ≤T3a based on MRI (if done); N0-Nx; M0-Mx (AJCC 7th Edition)
• Prostate-specific antigen (PSA) ≤ 80 ng/ml, obtained within 3 months.
• Patients belonging in the National Comprehensive Cancer Network (NCCN) high recurrence risk group. High risk: Clinical stage T3a, or Gleason score = 8-10, or PSA >20 ng/mL.
• Prostate volume: ≤ 80 cc on transrectal ultrasound
• IPSS score ≤15
• Zubrod performance status 0-2 or equivalent
• No prior total prostatectomy or cryotherapy of the prostate. Prior transurethral resection or laser ablation is permitted.
• No prior radiotherapy to the prostate or lower pelvis
• No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery, in the investigator's opinion
• No history of an invasive malignancy (other than this prostate cancer, or non-metastatic basal or squamous skin cancers) in the last 5 years
• No androgen deprivation therapy (ADT) can be prescribed prior to or during radiation therapy
• Must be able to have gold fiducial markers placed in the prostate or, if patient already has fiducial markers placed, they must be in accordance with the protocol specifications
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to fill out IPSS, SHIM, and EPIC quality of life forms
• Age ≥18 years
• IPSS (AUA) score ≤15

Exclusion Criteria:

• Does not have a diagnosis of prostate adenocarcinoma
• Has very low risk, low risk, intermediate risk or very high risk disease as defined by the NCCN
• Has stage N1 or M1 (metastatic) disease
• Has a PSA of greater than 80 ng/ml obtained no greater than 3 months prior to randomization
• Prostate volume greater than 80 cc on transrectal ultrasound
• Zubrod performance status 3 or greater
• Prior total prostatectomy or cryotherapy of the prostate
• Prior radiation therapy to the pelvis
• Implanted hardware which limits treatment planning or delivery (determined by the investigator).
• Diagnosis of an invasive malignancy within 5 years (other than current prostate cancer or non-metastatic basal or squamous skin cancers)
• The use of androgen deprivation therapy (ADT) prior to registration or during radiation
• Inability to have gold fiducial markers placed in the prostate, or fiducial markers already placed, that are not in accordance with the protocol
• Unwilling or inability to give informed consent
• Not willing to fill out IPSS, SHIM, and EPIC quality of life questionnaires
• IPSS score >15

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose Escalation of SBRT; Stereotactic Body Radiation Therapy (SBRT) followed by prostatectomy and Quality of Life questionnaires. The radiation will be given for only 5 days. Conventional radiation to the prostate is given over 7-8 weeks.

Radiation: Stereotactic Body Radiation Therapy (SBRT); The first group of patients to enter the study will receive 5 Gy of SBRT per day for 5 days, the second group will receive 6 Gy per day for 5 days. Each treatment will take about 3 minutes and be given as an outpatient at Moffitt Cancer Center.; Other Names: radiation therapy; Procedure: Prostatectomy; About 4-6 weeks after SBRT, participants will have a prostatectomy.; Other Names: surgery; Other: Quality of Life Questionnaires; Patient assessed health-related quality of life (HRQOL). Quality of Life (QOL) will be assessed using Prostate Symptom Score (IPSS), rectal assessment scale (RAS), sexual health inventory for men (SHIM), and Expanded Prostate Cancer Index Composite (EPIC) patient questionnaires: administered prior to SBRT, and at 2 weeks, 4 weeks, 2 months and then every 3 months up to 18 months post-prostatectomy.; Other Names: questionnaire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	Acute dose-limiting toxicity and quality of life due to preoperative SBRT followed by robotic-assisted laparoscopic radical prostatectomy at 14 ± 5 days and 28 ± 5 days post-prostatectomy in high risk prostate cancer patients. In order to assess the toxicity of preoperative SBRT, the severity of specific events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4 form where a score of ≥3 is considered dose-limiting.	Up to 28 ± 5 days post-prostatectomy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Late Toxicity	Late (defined as occurring more than 90 days after the start of radiotherapy) toxicity that is grade 2 or more as defined by the Common Terminology Criteria for Adverse Events version 4.	90+ days after start of radiotherapy
Mean Catheterization Time for Study Participants	Mean catheterization time for study participants, compared to existing mean statistics for robotic-assisted laparoscopic radical prostatectomy.	Up to 18 months post surgery
Mean Hospital Stay for Study Participants	Mean hospital stay for study participants, compared to existing mean statistics for robotic-assisted laparoscopic radical prostatectomy.	Up to 18 months post surgery
Reoperation Rate for Study Participants	Mean reoperation rate for study participants, compared to existing mean statistics for robotic-assisted laparoscopic radical prostatectomy.	Up to 18 months post surgery
Patient-Assessed Changes in Health-Related Quality of Life (HRQOL) - Expanded Prostate Cancer Index Composite (EPIC)	Administered prior to SBRT, and at 2 weeks, 4 weeks, 2 months and then every 3 months up to 18 months post-prostatectomy. The 26-item, short-form version of the Expanded Prostate Cancer Index Composite (EPIC) is a validated questionnaire used to assess HRQOL in prostate cancer patients. EPIC includes 4 domains: urinary, bowel, sexual, and hormonal. There are summary, i.e., overall, scores and function and bother subscale scores for each of the 4 domains. The urinary domain has 2 additional subscales: incontinence and irritative/obstructive. Domains and subscales are scored using a 0-100 grading system, with a higher score indicating a better quality of life.	Up to 18 months post surgery
Patient-Assessed Changes in HRQOL - International Prostate Symptom Score (IPSS)	Administered prior to SBRT, and at 2 weeks, 4 weeks, 2 months and then every 3 months up to 18 months post-prostatectomy. The IPSS will be used to assess changes in urinary toxicity. Scoring is 0, 1, 2, 3, 4, 5 per question, Total IPSS Score out of 35 points from 7 questions. Descriptive summaries of scores at baseline and each subsequent follow up will include means and standard deviations.	Up to 18 months post surgery
Patient-Assessed Changes in HRQOL - Rectal Assessment Scale (RAS)	Administered prior to SBRT, and at 2 weeks, 4 weeks, 2 months and then every 3 months up to 18 months post-prostatectomy. The RAS will be used to assess changes in rectal toxicity. Scoring is 0, 1, 2, 3 per question, Total RAS Score out of 15 points from 5 questions. Descriptive summaries of scores at baseline and each subsequent follow up will include means and standard deviations.	Up to 18 months post surgery
Patient-Assessed Changes in HRQOL - Sexual Health Inventory for Men (SHIM)	Administered prior to SBRT, and at 2 weeks, 4 weeks, 2 months and then every 3 months up to 18 months post-prostatectomy. The SHIM will be used to assess changes in sexual toxicity. Scoring is 0, 1, 2, 3, 4, 5 per question, Total SHIM score out of 25 points from 5 questions. Descriptive summaries of scores at baseline and each subsequent follow up will include means and standard deviations.	Up to 18 months post surgery

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Julio Pow-Sang, M.D., H. Lee Moffitt Cancer Center and Research Institute; Principal Investigator: Peter Johnstone, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2016
• Primary Completion (Actual): July 5, 2018
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 7, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Actual): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Quality of Life; Prostate Adenocarcinoma; Prostatectomy; Stereotactic Body Radiation Therapy (SBRT); High Risk Prostate Cancer; Preoperative SBRT
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: MCC-18201