COMPPARE: A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
|
Outcome Measures
Primary Outcome Measures
- Bowel urgency and bowel frequency Expanded Prostate Cancer Index Composite (EPIC) item scores [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
Secondary Outcome Measures
- Grade 2 or higher toxicity for each adverse event assessed by CTCAE [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.
- Grade 2 or higher toxicity for each adverse event assessed by PRO-CTCAE. [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.
- Freedom from biochemical progression using PSA results. [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).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of adenocarcinoma of the prostate.
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30-85 years of age at the time of consent with a life expectancy estimation (LEE) of ≥ 8 years.
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Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score, DRE with or without mpMRI, and clinical stage.
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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.
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If patient has high-risk disease, nuclear medicine bone imaging must be performed to document the absence of overt metastatic disease in bones.
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ECOG/Zubrod Performance Status 0 - 2.
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Candidate for definitive prostate radiotherapy (either IMRT or proton).
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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:
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Findings of metastatic disease (nodal or distant, N1 or M1).
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Very high-risk prostate cancer based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines.
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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].
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Previous prostate cancer treatment with the exception of ADT according to NCCN guidelines.
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History of invasive rectal malignancy or other malignancy in the true pelvis (e.g. bladder, rectum, or reproductive organs), regardless of disease-free interval.
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Active inflammatory bowel disease (i.e., patients requiring medical interventions or who are symptomatic).
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Prior pelvic RT for any reason.
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Documented lack of psychological ability or general health permitting completion of the study requirements and required follow-up.
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of Alabama at Birmingham (UAB) | Birmingham | Alabama | United States | 35294 |
2 | University of Arizona | Tucson | Arizona | United States | 85724 |
3 | University of California San Diego | La Jolla | California | United States | 92093 |
4 | Proton Therapy Treatment Center - Loma Linda University | Loma Linda | California | United States | 92354 |
5 | Kaiser Permanente | Los Angeles | California | United States | 90027 |
6 | Sutter Health | Roseville | California | United States | 95661 |
7 | California Protons Cancer Therapy Center | San Diego | California | United States | 92121 |
8 | Department of Radiation Oncology Davis Cancer Pavilion | Gainesville | Florida | United States | 32611 |
9 | University of Florida Proton Therapy Institute | Jacksonville | Florida | United States | 32206 |
10 | Ackerman Cancer Center | Jacksonville | Florida | United States | 32223 |
11 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
12 | University of Miami School of Medicine | Miami | Florida | United States | 33136 |
13 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
14 | Orlando Health UF Health Center | Orlando | Florida | United States | 32806 |
15 | Winship Cancer Institute - Emory University | Atlanta | Georgia | United States | 30322 |
16 | University of Chicago | Chicago | Illinois | United States | 60637 |
17 | Northwestern Medicine Proton Center | Warrenville | Illinois | United States | 60555 |
18 | University of Kansas Medical Center | Lawrence | Kansas | United States | 66045 |
19 | University of Louisville | Louisville | Kentucky | United States | 40292 |
20 | Willis-Knighton Medical Center PTC | Shreveport | Louisiana | United States | 71103 |
21 | Johns Hopkins University | Baltimore | Maryland | United States | 21218 |
22 | University of Maryland | College Park | Maryland | United States | 20742 |
23 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
24 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
25 | Mayo Clinic Health System | Mankato | Minnesota | United States | 56001 |
26 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
27 | S Lee Kling Proton Therapy Center - Washington University Medical Center | Saint Louis | Missouri | United States | 63110 |
28 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08901 |
29 | ProCure Proton Therapy Center | Somerset | New Jersey | United States | 08873 |
30 | New York Proton Center | New York | New York | United States | 10035 |
31 | Weill Cornell | New York | New York | United States | 10065 |
32 | The Univeristy of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
33 | The Duke University Health System | Durham | North Carolina | United States | 27705 |
34 | UNC- Rex Hospital | Raleigh | North Carolina | United States | 27607 |
35 | University of Cincinnati Medical PTC | Cincinnati | Ohio | United States | 45267 |
36 | Cleveland Clinic | Cleveland | Ohio | United States | 44106 |
37 | University Hospitals- Seidman Cancer Center | Cleveland | Ohio | United States | 44106 |
38 | Stephenson Cancer Center | Oklahoma City | Oklahoma | United States | 73104 |
39 | Oregon Health & Science University | Portland | Oregon | United States | 97201 |
40 | University of Pennsylvania--Penn Medicine | Philadelphia | Pennsylvania | United States | 19104 |
41 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19144 |
42 | Medical University of South Carolina | Charleston | South Carolina | United States | 29407 |
43 | Mabry Center for Cancer Care | Orangeburg | South Carolina | United States | 29118 |
44 | Provision CARES Proton Therapy Center Knoxville | Knoxville | Tennessee | United States | 37909 |
45 | Texas Oncology | Austin | Texas | United States | 78731 |
46 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
47 | Texas Center for Proton Therapy | Irving | Texas | United States | 75063 |
48 | Texas Oncology - Longview | Longview | Texas | United States | 75601 |
49 | Texas Oncology - McKinney | McKinney | Texas | United States | 75071 |
50 | Texas Oncology - Plano West | Plano | Texas | United States | 75093 |
51 | Texas Oncology - Waco | Waco | Texas | United States | 76712 |
52 | University of Virginia | Charlottesville | Virginia | United States | 22904 |
53 | Inova Schar Cancer Institute | Fairfax | Virginia | United States | 22031 |
54 | Hampton University Proton Therapy Institute | Hampton | Virginia | United States | 23666 |
55 | Seattle Care Alliance/University of Washington | Seattle | Washington | United States | 98133 |
56 | Mayo Clinic Health System | Eau Claire | Wisconsin | United States | 54703 |
57 | Mayo Clinic Health System-Franciscan Healthcare | Sparta | Wisconsin | United States | 54656 |
Sponsors and Collaborators
- University of Florida
- Patient-Centered Outcomes Research Institute
Investigators
- Principal Investigator: Nancy P. Mendenhall, MD, University of Florida
Study Documents (Full-Text)
None provided.More Information
Publications
- AJCC Cancer Staging Manual. 8th ed. Cham, Switzerland: Springer International Publishing; 2017.
- Bryant C, Smith TL, Henderson RH, Hoppe BS, Mendenhall WM, Nichols RC, Morris CG, Williams CR, Su Z, Li Z, Lee D, Mendenhall NP. Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):422-434. doi: 10.1016/j.ijrobp.2016.02.038. Epub 2016 Feb 16.
- Chamie K, Williams SB, Hu JC. Population-Based Assessment of Determining Treatments for Prostate Cancer. JAMA Oncol. 2015 Apr;1(1):60-7. doi: 10.1001/jamaoncol.2014.192.
- Chen RC, Clark JA, Talcott JA. Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function. J Clin Oncol. 2009 Aug 20;27(24):3916-22. doi: 10.1200/JCO.2008.18.6486. Epub 2009 Jul 20.
- Friedland W, Schmitt E, Kundrát P, Dingfelder M, Baiocco G, Barbieri S, Ottolenghi A. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Sci Rep. 2017 Mar 27;7:45161. doi: 10.1038/srep45161.
- Gray PJ, Lin CC, Cooperberg MR, Jemal A, Efstathiou JA. Temporal Trends and the Impact of Race, Insurance, and Socioeconomic Status in the Management of Localized Prostate Cancer. Eur Urol. 2017 May;71(5):729-737. doi: 10.1016/j.eururo.2016.08.047. Epub 2016 Sep 3.
- Grosse N, Fontana AO, Hug EB, Lomax A, Coray A, Augsburger M, Paganetti H, Sartori AA, Pruschy M. Deficiency in homologous recombination renders Mammalian cells more sensitive to proton versus photon irradiation. Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):175-81. doi: 10.1016/j.ijrobp.2013.09.041. Epub 2013 Nov 13.
- Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
- Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134.
- Mendenhall NP, Hoppe BS, Nichols RC, Mendenhall WM, Morris CG, Li Z, Su Z, Williams CR, Costa J, Henderson RH. Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014 Mar 1;88(3):596-602. doi: 10.1016/j.ijrobp.2013.11.007.
- Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016 Jul;66(4):271-89. doi: 10.3322/caac.21349. Epub 2016 Jun 2.
- NCCN Clinical Practical Guidelines in Oncology: Prostate Cancer. Version 2. 2018.
- Resnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, Hoffman RM, Potosky AL, Stanford JL, Stroup AM, Van Horn RL, Penson DF. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013 Jan 31;368(5):436-45. doi: 10.1056/NEJMoa1209978.
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- Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A, Klein E, Kibel A, Pisters LL, Kuban D, Kaplan I, Wood D, Ciezki J, Shah N, Wei JT. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008 Mar 20;358(12):1250-61. doi: 10.1056/NEJMoa074311.
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- Tommasino F, Durante M. Proton radiobiology. Cancers (Basel). 2015 Feb 12;7(1):353-81. doi: 10.3390/cancers7010353. Review.
- Trofimov A, Nguyen PL, Coen JJ, Doppke KP, Schneider RJ, Adams JA, Bortfeld TR, Zietman AL, Delaney TF, Shipley WU. Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):444-53. Epub 2007 May 21.
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- Vargas C, Fryer A, Mahajan C, Indelicato D, Horne D, Chellini A, McKenzie C, Lawlor P, Henderson R, Li Z, Lin L, Olivier K, Keole S. Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):744-51. Epub 2007 Sep 27.
- Waddle MR, Sio TT, Van Houten HK, Foote RL, Keole SR, Schild SE, Laack N, Daniels TB, Crown W, Shah ND, Miller RC. Photon and Proton Radiation Therapy Utilization in a Population of More Than 100 Million Commercially Insured Patients. Int J Radiat Oncol Biol Phys. 2017 Dec 1;99(5):1078-1082. doi: 10.1016/j.ijrobp.2017.07.042. Epub 2017 Aug 2.
- Winter M, Dokic I, Schlegel J, Warnken U, Debus J, Abdollahi A, Schnölzer M. Deciphering the Acute Cellular Phosphoproteome Response to Irradiation with X-rays, Protons and Carbon Ions. Mol Cell Proteomics. 2017 May;16(5):855-872. doi: 10.1074/mcp.M116.066597. Epub 2017 Mar 16.
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- COMPPARE
- PCORI-6312
- IRB201801001
- OCR17881