Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer
NCT ID: NCT03801876
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
300 participants
INTERVENTIONAL
2019-06-26
2031-12-21
Brief Summary
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Detailed Description
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I. To determine if overall survival (OS) is improved with proton beam radiation therapy (PBT) treatment as compared to intensity modulated photon radiation therapy (IMRT) as part of planned protocol treatment for patients with esophageal cancer.
II. To determine if OS with PBT is non-inferior to IMRT as part of planned protocol treatment and that there will be less grade 3+ cardiopulmonary toxicity with PBT than with IMRT.
SECONDARY OBJECTIVES:
I. To compare the symptom burden and impact on functioning of patients between treatment modalities based on Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI) and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue.
II. To compare the Quality-Adjusted Life Years (QALY) using EuroQol five-dimensional questionnaire (EQ5D) as a health outcome between PBT and IMRT, if the protocol primary endpoint is met.
III. To assess the pathologic response rate between PBT and IMRT. IV. To assess the cost-benefit economic analysis of treatment between radiation modalities.
V. To compare the length of hospitalization after protocol surgery between PBT and IMRT.
VI. To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT.
VII. To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT \& IMRT.
VIII. To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT.
IX. To compare incidence of both early (\< 90 days from treatment start) and late (≥ 90 days from treatment start) cardiovascular and pulmonary events between PBT versus IMRT.
X. To compare the total toxicity burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.
EXPLORATORY OBJECTIVES:
I. To collect biospecimens for future analyses, for example to assess cardiac and inflammatory biomarkers in association with treatment complications.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive chemotherapy consisting of carboplatin/paclitaxel, or fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX)/capecitabine-oxaliplatin (CAPOX), or docetaxel/fluorouracil (5-FU, with capecitabine an acceptable substitute for 5-FU), as determined by the patient and their treating physician while undergoing PBT.
GROUP II: Patients 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.
In both groups, within 4-8 weeks after completion of chemotherapy and radiation therapy, patients should undergo an esophagectomy if it's determined that the patient can tolerate an esophagectomy and whether the tumor is surgically resectable.
Additionally, patients undergo blood sample collection, and positron emission tomography (PET)/computed tomography (CT) or CT throughout the study.
After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually thereafter.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group I (PBT, concurrent chemotherapy, esophagectomy)
Patients 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.
Biospecimen Collection
Undergo blood sample collection
Capecitabine
Oral
Carboplatin
Given IV
Computed Tomography
Undergo CT or PET/CT
Docetaxel
IV
Esophagectomy
Undergo esophagectomy
Fluorouracil
IV
Leucovorin Calcium
Oral
Oxaliplatin
IV
Paclitaxel
Given IV
Positron Emission Tomography
Undergo PET/CT
Proton Beam Radiation Therapy
Undergo PBT
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Group II (IMRT, concurrent chemotherapy, esophagectomy)
Patients 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.
Biospecimen Collection
Undergo blood sample collection
Capecitabine
Oral
Carboplatin
Given IV
Computed Tomography
Undergo CT or PET/CT
Docetaxel
IV
Esophagectomy
Undergo esophagectomy
Fluorouracil
IV
Intensity-Modulated Radiation Therapy
Undergo IMRT
Leucovorin Calcium
Oral
Oxaliplatin
IV
Paclitaxel
Given IV
Positron Emission Tomography
Undergo PET/CT
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Interventions
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Biospecimen Collection
Undergo blood sample collection
Capecitabine
Oral
Carboplatin
Given IV
Computed Tomography
Undergo CT or PET/CT
Docetaxel
IV
Esophagectomy
Undergo esophagectomy
Fluorouracil
IV
Intensity-Modulated Radiation Therapy
Undergo IMRT
Leucovorin Calcium
Oral
Oxaliplatin
IV
Paclitaxel
Given IV
Positron Emission Tomography
Undergo PET/CT
Proton Beam Radiation Therapy
Undergo PBT
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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)
* For patients who DID NOT receive induction chemotherapy: ANC ≥ 1,500 cells/mm\^3
* For patients who DID receive induction chemotherapy: ANC ≥ 1,000 cells/mm\^3
* Platelets (within 30 days prior to Step 1 registration)
* For patients who DID NOT receive induction chemotherapy: Platelets ≥ 100,000/uL
* For patients who DID receive induction chemotherapy: Platelets ≥ 75,000/uL
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable) (within 30 days prior to Step 1 registration)
* Serum creatinine ≤ 1.5 X upper limit of normal (ULN) or creatinine clearance \> 40 mL/min estimated by Cockcroft-Gault formula (within 30 days prior to Step 1 registration)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 30 days prior to Step 1 registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (within 30 days prior to Step 1 registration)
* Negative pregnancy test (serum or urine) within 14 days prior to Step 1 registration for women of child bearing potential
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria
* 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
* Human immunodeficiency virus (HIV) positive with CD4 count \< 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
* PRIOR TO STEP 2 REGISTRATION:
* Unable to obtain confirmation of payment coverage (insurance or other) for either possible radiation treatment
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
NRG Oncology
OTHER
Responsible Party
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Principal Investigators
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Steven H Lin
Role: PRINCIPAL_INVESTIGATOR
NRG Oncology
Locations
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Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Miami Cancer Institute
Miami, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Emory Proton Therapy Center
Atlanta, Georgia, United States
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Alton Memorial Hospital
Alton, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Memorial Hospital East
Shiloh, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
Maryland Proton Treatment Center
Baltimore, Maryland, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
UM Upper Chesapeake Medical Center
Bel Air, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
McLaren Cancer Institute-Bay City
Bay City, Michigan, United States
Corewell Health Dearborn Hospital
Dearborn, Michigan, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, United States
McLaren Cancer Institute-Flint
Flint, Michigan, United States
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, United States
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, United States
McLaren Cancer Institute-Owosso
Owosso, Michigan, United States
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, United States
Corewell Health Beaumont Troy Hospital
Troy, Michigan, United States
Mayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, United States
Mercy Hospital
Coon Rapids, Minnesota, United States
Unity Hospital
Fridley, Minnesota, United States
Mayo Clinic Health Systems-Mankato
Mankato, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
Mayo Clinic Radiation Therapy-Northfield
Northfield, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Ridgeview Medical Center
Waconia, Minnesota, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Mercy Hospital Springfield
Springfield, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital South
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
New York Proton Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, United States
Geauga Hospital
Chardon, Ohio, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Case Western Reserve University
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Mercy Cancer Center-Elyria
Elyria, Ohio, United States
UH Seidman Cancer Center at Landerbrook Health Center
Mayfield Heights, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, United States
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights, Ohio, United States
University Hospitals Parma Medical Center
Parma, Ohio, United States
University Hospitals Portage Medical Center
Ravenna, Ohio, United States
UH Seidman Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, United States
University Hospitals Sharon Health Center
Wadsworth, Ohio, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, United States
UHHS-Westlake Medical Center
Westlake, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Thompson Proton Center
Knoxville, Tennessee, United States
Thompson Cancer Survival Center
Knoxville, Tennessee, United States
Thompson Cancer Survival Center - West
Knoxville, Tennessee, United States
Thompson Oncology Group-Maryville
Maryville, Tennessee, United States
Thompson Oncology Group-Oak Ridge
Oak Ridge, Tennessee, United States
MD Anderson in The Woodlands
Conroe, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
MD Anderson West Houston
Houston, Texas, United States
MD Anderson League City
League City, Texas, United States
MD Anderson in Sugar Land
Sugar Land, Texas, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Inova Alexandria Hospital
Alexandria, Virginia, United States
Inova Schar Cancer Institute
Fairfax, Virginia, United States
Inova Fair Oaks Hospital
Fairfax, Virginia, United States
Inova Loudoun Hospital
Leesburg, Virginia, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2018-03378
Identifier Type: REGISTRY
Identifier Source: secondary_id
NRG-GI006
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-GI006
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-GI006
Identifier Type: -
Identifier Source: org_study_id