A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer (COMPPARE)

March 5, 2026 updated by: University of Florida
This study is a large, prospective, pragmatic, controlled comparison of patient-centric outcomes [quality of life (QOL), toxicity, and disease control] between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a large, prospective, pragmatic, controlled comparison of patient-centric outcomes [quality of life (QOL), toxicity, and disease control] between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques. This study includes a pre-specified randomized comparison of standard fractionation and moderate hypofractionation dose schemes within the proton therapy cohort. In addition, subgroup analyses will include a comparison of outcomes by race (Black vs. White), comorbidity score (0 vs. 1+), age (<65 vs. ≥65), fractionation schedule (standard, moderate, ultra-hypofractionation), and prostate cancer aggressiveness (very low and low, intermediate, and high risk) for all objectives.

All interventions will be standard of care (SOC) radiation strategies using either IMRT or proton therapy. All patient-reported QOL, patient-scored and patient-reported toxicity, and disease control assessments will be SOC. Participants will also complete pretreatment surveys regarding demographic data, personal treatment goals, factors affecting treatment decision-making, and sources of information used in treatment selection.

Study Type

Interventional

Enrollment (Estimated)

3000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham (UAB)
    • California
      • La Jolla, California, United States, 92093
        • University Of California San Diego
      • Loma Linda, California, United States, 92354
        • Proton Therapy Treatment Center - Loma Linda University
      • Roseville, California, United States, 95661
        • Sutter Health
      • San Diego, California, United States, 92121
        • California Protons Cancer Therapy Center
    • Florida
      • Gainesville, Florida, United States, 32611
        • Department of Radiation Oncology Davis Cancer Pavilion
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Jacksonville, Florida, United States, 32206
        • University of Florida Proton Therapy Institute
      • Jacksonville, Florida, United States, 32223
        • Ackerman Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Miami, Florida, United States, 33136
        • University of Miami School of Medicine
      • Orlando, Florida, United States, 32806
        • Orlando Health UF Health Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute - Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Proton Center
    • Kansas
      • Lawrence, Kansas, United States, 66045
        • University Of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40292
        • University of Louisville
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Willis-Knighton Medical Center PTC
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Johns Hopkins University
      • College Park, Maryland, United States, 20742
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Mankato, Minnesota, United States, 56001
        • Mayo Clinic Health System
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63110
        • S Lee Kling Proton Therapy Center - Washington University Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute of New Jersey
      • Somerset, New Jersey, United States, 08873
        • Covenant Health
    • New York
      • New York, New York, United States, 10035
        • New York Proton Center
      • New York, New York, United States, 10065
        • Weill Cornell
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • The Duke University Health System
      • Raleigh, North Carolina, United States, 27607
        • UNC- Rex Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati Medical PTC
      • Cleveland, Ohio, United States, 44106
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals- Seidman Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97201
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania--Penn Medicine
      • Philadelphia, Pennsylvania, United States, 19144
        • Thomas Jefferson University
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • Medical University of South Carolina
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Covenant Health Proton Center
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
      • Irving, Texas, United States, 75063
        • Texas Center for Proton Therapy
      • Longview, Texas, United States, 75601
        • Texas Oncology - Longview
      • McKinney, Texas, United States, 75071
        • Texas Oncology - McKinney
      • Plano, Texas, United States, 75093
        • Texas Oncology - Plano West
      • Waco, Texas, United States, 76712
        • Texas Oncology - Waco
    • Virginia
      • Charlottesville, Virginia, United States, 22904
        • University of Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Hampton, Virginia, United States, 23666
        • Hampton University Proton Therapy Institute
    • Washington
      • Seattle, Washington, United States, 98133
        • Seattle Care Alliance/University of Washington
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54703
        • Mayo Clinic Health System
      • Sparta, Wisconsin, United States, 54656
        • Mayo Clinic Health System-Franciscan Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of adenocarcinoma of the prostate.
  • 30-85 years of age at the time of consent with a life expectancy estimation (LEE) of ≥ 8 years.
  • Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score, DRE with or without mpMRI, and clinical stage.
  • Very low-risk, low-risk, intermediate-risk, or high-risk disease based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.
  • If patient has high-risk disease, nuclear medicine bone imaging must be performed to document the absence of overt metastatic disease in bones.
  • ECOG/Zubrod Performance Status 0 - 2.
  • Candidate for definitive prostate radiotherapy (either IMRT or proton).
  • If patient is to be treated with IMRT, all treatment must be planned with IMRT; if patient is to be treated with protons, all treatment must be planned with protons (including pelvic nodes if treated).

Exclusion Criteria:

  • Findings of metastatic disease (nodal or distant, N1 or M1).
  • Very high-risk prostate cancer based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.
  • Prior procedures for treatment of prostate cancer, such as radical or robotic prostatectomy, high-intensity focused ultrasound, cryosurgery, or focal prostatectomy [note that procedures used for benign prostatic hyperplasia symptoms, such as transurethral resection of the prostate (TURP) and GreenLight Laser Therapy, are acceptable].
  • Previous prostate cancer treatment with the exception of ADT according to NCCN guidelines.
  • History of invasive rectal malignancy or other malignancy in the true pelvis (e.g. bladder, rectum, or reproductive organs), regardless of disease-free interval.
  • Active inflammatory bowel disease (i.e., patients requiring medical interventions or who are symptomatic).
  • Prior pelvic RT for any reason.
  • Documented lack of psychological ability or general health permitting completion of the study requirements and required follow-up.
  • Documented diminished capacity to understand the risks and benefits of participation in research and to autonomously provide informed consent.

In addition, because the embedded randomized controlled trial compares fractionation schemes, patients who are receiving pelvic node irradiation may not be enrolled on the randomized controlled trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IMRT (Photon)
As this trial is pragmatic, all treatment will be standard of care.
Radiation: Standard of Care IMRT (Photon)
As this trial is pragmatic, all treatment will be standard of care.
Active Comparator: Proton Therapy Standard of Care
As this trial is pragmatic, all treatment will be standard of care.
Radiation: Standard of Care Proton Therapy
As this trial is pragmatic, all treatment will be standard of care.
Experimental: Standard Proton Therapy
78.0 Gy (RBE) in 39 fractions. This is Arm 1 of the embedded randomized trial.
Radiation: Proton Arm 1: Standard Proton Therapy
78.0 Gy (RBE) in 39 fractions
Experimental: Hypofractionated Proton therapy
60.0 Gy (RBE) in 20 fractions This is Arm 2 of the embedded randomized trial.
Radiation: Proton Arm 2: Hypofractionated Proton Therapy
60.0 Gy (RBE) in 20 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bowel urgency and bowel frequency Expanded Prostate Cancer Index Composite (EPIC) item scores
Time Frame: 2-years after the end of radiation therapy
EPIC assesses the disease-specific aspects of prostate cancer and its therapies and comprises four summary domains (Urinary, Bowel, Sexual and Hormonal). Factor analysis supports dividing the Urinary Domain Summary Score into two distinct Incontinence and Irritative/Obstructive subscales. In addition, each Domain Summary Score has measurable Function Subscale and Bother Subscale components. Response options for each EPIC item form a Likert scale, and multi-item scale scores are components. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL
2-years after the end of radiation therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grade 2 or higher toxicity for each adverse event assessed by CTCAE
Time Frame: 2-years after the end of radiation therapy
The NCI Common Terminology Criteria for Adverse Events v5.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.
2-years after the end of radiation therapy
Grade 2 or higher toxicity for each adverse event assessed by PRO-CTCAE.
Time Frame: 2-years after the end of radiation therapy
PRO-CTCAE responses are scored from 0 to 4, and there are as yet no standardized scoring rules for how to combine attributes into a single score or how best to analyse PRO-CTCAE data longitudinally. PRO-CTCAE scores for each attribute (frequency, severity and/or interference) should be presented descriptively (e.g. summary statistics or graphical presentations). CTCAE grades for the corresponding time period should be presented in conjunction with PRO-CTCAE scores.
2-years after the end of radiation therapy
Freedom from biochemical progression using PSA results.
Time Frame: 3-years after the end of radiation therapy
Biochemical failure is defined as a sustained rise in PSA of 2 ng/mL or more above the nadir (the lowest PSA level after radiotherapy).
3-years after the end of radiation therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

Patient-Centered Outcomes Research Institute

Investigators

  • Principal Investigator: Nancy P. Mendenhall, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2018

Primary Completion (Actual)

February 15, 2026

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

May 15, 2018

First Submitted That Met QC Criteria

June 7, 2018

First Posted (Actual)

June 19, 2018

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 5, 2026

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COMPPARE
  • PCORI-6312 (Other Grant/Funding Number: PCORI)
  • IRB201801001 (Other Identifier: University of Florida)
  • OCR17881 (Other Identifier: University of Florida)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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