Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer
Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
4 other identifiers
interventional
300
1 country
95
Brief Summary
This trial studies how well proton beam radiation therapy compared with intensity modulated photon radiotherapy works in treating patients with stage I-IVA esophageal cancer. Proton beam radiation therapy uses a beam of protons (rather than x-rays) to send radiation inside the body to the tumor without damaging much of the healthy tissue around it. Intensity modulated photon radiotherapy uses high-energy x-rays to deliver radiation directly to the tumor without damaging much of the healthy tissue around it. It is not yet known whether proton beam therapy or intensity modulated photon radiotherapy will work better in treating patients with esophageal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2019
Longer than P75 for phase_3
95 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 3, 2019
CompletedFirst Posted
Study publicly available on registry
January 14, 2019
CompletedStudy Start
First participant enrolled
June 26, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 21, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 21, 2031
May 7, 2026
April 1, 2026
7.5 years
January 3, 2019
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Overall survival (OS)
Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test.
From the date of randomization to the date of death due to any cause or date of last follow-up for patients without an OS event reported. This analysis occurs after 173 deaths; estimated to occur 4 years after accrual completion
Incidence of specific grade 3+ cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatment
Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Difference in proportion of defined cardiopulmonary AEs will be analyzed with a chi-squared test.
From baseline up to 8 years
Secondary Outcomes (10)
Change in patient reported outcomes (PROs) of symptom and function
Baseline up to 12 months after end of chemoradiation
Pathologic response rate
At time of surgery
Length of hospitalization
From baseline up to 8 years
Grade 4 lymphopenia during chemoradiation
From baseline up to 8 years
Lymphocyte counts
From baseline up to 8 years
- +5 more secondary outcomes
Study Arms (2)
Group I (PBT, concurrent chemotherapy, esophagectomy)
EXPERIMENTALPatients undergo PBT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive chemotherapy consisting of carboplatin/paclitaxel, or FOLFOX/CAPOX, or docetaxel/5-FU (with capecitabine an acceptable substitute for 5-FU) as determined by the patient and their treating physician while undergoing PBT. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study.
Group II (IMRT, concurrent chemotherapy, esophagectomy)
ACTIVE COMPARATORPatients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive chemotherapy consisting of carboplatin/paclitaxel, or FOLFOX/CAPOX, or docetaxel/5-FU (with capecitabine an acceptable substitute for 5-FU) as determined by the patient and their treating physician while undergoing IMRT. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study.
Interventions
Undergo blood sample collection
Oral
Given IV
Undergo CT or PET/CT
IV
Undergo esophagectomy
IV
Undergo IMRT
Oral
IV
Given IV
Undergo PET/CT
Undergo PBT
Ancillary studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- PRIOR TO STEP 1 REGISTRATION:
- Histologically proven diagnosis of adenocarcinoma or squamous cell carcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II)
- Stage I-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition based on the following diagnostic workup:
- History/physical examination
- Whole-body fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) with or without contrast (preferred) or chest/abdominal (include pelvic if clinically indicated) CT with contrast
- For patients who DID NOT receive induction chemotherapy, scan must occur within 30 days prior to Step 1 registration
- For patients who DID receive induction chemotherapy, scan must occur:
- Within 30 days after final induction chemotherapy dose; OR
- Within 30 days prior to Step 1 registration
- Note: Patients who had prior endoscopic mucosal resection (EMR) with a diagnosis of AJCC stage I-IVA, excluding T4b, esophageal cancer are eligible
- Surgical consultation to determine whether or not the patient is a candidate for resection after completion of chemoradiation
- Induction chemotherapy for the current malignancy prior to concurrent chemoradiation allowed if last dose is no more than 90 days and no less than 10 days prior to Step 1 registration; only FOLFOX, CAPOX, durvalumab-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) (D-FLOT) and FLOT will be allowed as the induction chemotherapy regimen
- Age ≥ 18
- Zubrod performance status 0, 1, or 2
- Absolute neutrophil count (ANC) (within 30 days prior to Step 1 registration)
- +11 more criteria
You may not qualify if:
- Cervical esophageal cancers arisen from 15-18 cm from the incisors
- Patients with T4b disease according to the AJCC 8th edition
- Definitive clinical or radiologic evidence of metastatic disease
- Any active malignancy within 2 years of study registration that may alter the course of esophageal cancer treatment
- Prior thoracic radiotherapy that would result in overlap of radiation therapy fields
- Severe, active co-morbidity defined as follows:
- Active uncontrolled infection requiring IV antibiotics at the time of Step 1 registration
- Uncontrolled symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia not controlled by any device or medication at the time of Step 1 registration
- Myocardial infarction within 3 months prior to Step 1 registration
- Pregnant and/or nursing females
- PRIOR TO STEP 2 REGISTRATION:
- Unable to obtain confirmation of payment coverage (insurance or other) for either possible radiation treatment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
- National Cancer Institute (NCI)collaborator
Study Sites (95)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Emory Proton Therapy Center
Atlanta, Georgia, 30308, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Alton Memorial Hospital
Alton, Illinois, 62002, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Maryland Proton Treatment Center
Baltimore, Maryland, 21201, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706, United States
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
McLaren Cancer Institute-Flint
Flint, Michigan, 48532, United States
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910, United States
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446, United States
McLaren Cancer Institute-Owosso
Owosso, Michigan, 48867, United States
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073, United States
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085, United States
Mayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, 56007, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Mayo Clinic Health Systems-Mankato
Mankato, Minnesota, 56001, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Mayo Clinic Radiation Therapy-Northfield
Northfield, Minnesota, 55057, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
East White Plains, New York, 10604, United States
New York Proton Center
New York, New York, 10035, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122, United States
Geauga Hospital
Chardon, Ohio, 44024, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Mercy Cancer Center-Elyria
Elyria, Ohio, 44035, United States
UH Seidman Cancer Center at Landerbrook Health Center
Mayfield Heights, Ohio, 44124, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060, United States
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights, Ohio, 44130, United States
University Hospitals Parma Medical Center
Parma, Ohio, 44129, United States
University Hospitals Portage Medical Center
Ravenna, Ohio, 44266, United States
UH Seidman Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, 44870, United States
University Hospitals Sharon Health Center
Wadsworth, Ohio, 44281, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, 44145, United States
UHHS-Westlake Medical Center
Westlake, Ohio, 44145, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Covenant Health Proton Center
Knoxville, Tennessee, 37909, United States
Covenant Health Cancer Centers
Knoxville, Tennessee, 37916, United States
Covenant Health Cancer Centers - West
Knoxville, Tennessee, 37932, United States
Covenant Health Oncology Group - Maryville
Maryville, Tennessee, 37804, United States
Covenant Health Oncology Group - Oak Ridge
Oak Ridge, Tennessee, 37830, United States
MD Anderson in The Woodlands
Conroe, Texas, 77384, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MD Anderson West Houston
Houston, Texas, 77079, United States
MD Anderson League City
League City, Texas, 77573, United States
MD Anderson in Sugar Land
Sugar Land, Texas, 77478, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Inova Alexandria Hospital
Alexandria, Virginia, 22304, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033, United States
Inova Loudoun Hospital
Leesburg, Virginia, 20176, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701, United States
Related Publications (1)
Muijs CT, Klaver YLB, Nuyttens J, Lips IM, Muller K, Ebrahimi GM, Dankers FJWM, Verhoeven R, Schuit E, Berbee M. National indication protocol for proton radiotherapy in esophageal cancer patients in the Netherlands. Radiother Oncol. 2025 Dec;213:111164. doi: 10.1016/j.radonc.2025.111164. Epub 2025 Sep 24.
PMID: 41005671DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Steven H Lin
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 3, 2019
First Posted
January 14, 2019
Study Start
June 26, 2019
Primary Completion (Estimated)
December 21, 2026
Study Completion (Estimated)
December 21, 2031
Last Updated
May 7, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.