Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

August 20, 2026 updated by: NRG Oncology

Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

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
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital in Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic in Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Doral, Florida, United States, 33166
        • UM Sylvester Comprehensive Cancer Center at Doral
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Miami, Florida, United States, 33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Plantation, Florida, United States, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30308
        • Emory Proton Therapy Center
    • Illinois
      • Alton, Illinois, United States, 62002
        • Alton Memorial Hospital
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Shiloh, Illinois, United States, 62269
        • Memorial Hospital East
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Baltimore, Maryland, United States, 21201
        • Maryland Proton Treatment Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Bay City, Michigan, United States, 48706
        • McLaren Cancer Institute-Bay City
      • Dearborn, Michigan, United States, 48124
        • Corewell Health Dearborn Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Lansing, Michigan, United States, 48910
        • Karmanos Cancer Institute at McLaren Greater Lansing
      • Lapeer, Michigan, United States, 48446
        • McLaren Cancer Institute-Lapeer Region
      • Mount Pleasant, Michigan, United States, 48858
        • McLaren Cancer Institute-Central Michigan
      • Owosso, Michigan, United States, 48867
        • McLaren Cancer Institute-Owosso
      • Royal Oak, Michigan, United States, 48073
        • Corewell Health William Beaumont University Hospital
      • Troy, Michigan, United States, 48085
        • Corewell Health Beaumont Troy Hospital
    • Minnesota
      • Albert Lea, Minnesota, United States, 56007
        • Mayo Clinic Health System in Albert Lea
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Mankato, Minnesota, United States, 56001
        • Mayo Clinic Health Systems-Mankato
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology PA-Maplewood
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Northfield, Minnesota, United States, 55057
        • Mayo Clinic Radiation Therapy-Northfield
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63136
        • Siteman Cancer Center at Christian Hospital
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • St Louis, Missouri, United States, 63128
        • Mercy Hospital South
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10035
        • New York Proton Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • Ohio
      • Avon, Ohio, United States, 44011
        • UH Seidman Cancer Center at UH Avon Health Center
      • Beachwood, Ohio, United States, 44122
        • UHHS-Chagrin Highlands Medical Center
      • Chardon, Ohio, United States, 44024
        • Geauga Hospital
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Elyria, Ohio, United States, 44035
        • Mercy Cancer Center-Elyria
      • Mayfield Heights, Ohio, United States, 44124
        • UH Seidman Cancer Center at Landerbrook Health Center
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Middleburg Heights, Ohio, United States, 44130
        • UH Seidman Cancer Center at Southwest General Hospital
      • Parma, Ohio, United States, 44129
        • University Hospitals Parma Medical Center
      • Ravenna, Ohio, United States, 44266
        • University Hospitals Portage Medical Center
      • Sandusky, Ohio, United States, 44870
        • UH Seidman Cancer Center at Firelands Regional Medical Center
      • Wadsworth, Ohio, United States, 44281
        • University Hospitals Sharon Health Center
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
      • Westlake, Ohio, United States, 44145
        • UH Seidman Cancer Center at Saint John Medical Center
      • Westlake, Ohio, United States, 44145
        • UHHS-Westlake Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Covenant Health Cancer Centers
      • Knoxville, Tennessee, United States, 37932
        • Covenant Health Cancer Centers - West
      • Knoxville, Tennessee, United States, 37909
        • Covenant Health Proton Center
      • Maryville, Tennessee, United States, 37804
        • Covenant Health Oncology Group - Maryville
      • Oak Ridge, Tennessee, United States, 37830
        • Covenant Health Oncology Group - Oak Ridge
    • Texas
      • Conroe, Texas, United States, 77384
        • MD Anderson in The Woodlands
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
      • Houston, Texas, United States, 77079
        • MD Anderson West Houston
      • League City, Texas, United States, 77573
        • UT MD Anderson - League City
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Alexandria, Virginia, United States, 22304
        • Inova Alexandria Hospital
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Fairfax, Virginia, United States, 22033
        • Inova Fair Oaks Hospital
      • Leesburg, Virginia, United States, 20176
        • Inova Loudoun Hospital
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center - Montlake
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Mayo Clinic Health System-Eau Claire Clinic

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

    • 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:

  • 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
  • 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

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • JM8
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol Konzentrat
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Fluorouracil
IV
Other Names:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Drug: Oxaliplatin
IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • Ai Heng
  • Aiheng
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669
  • SR96669
  • Elplat
  • JM 83
  • JM83
  • RP54780
  • SR 96669
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Esophagectomy
Undergo esophagectomy
Other Names:
  • excision of the esophagus
Radiation: Proton Beam Radiation Therapy
Undergo PBT
Other Names:
  • Proton Radiation Therapy
  • PBRT
  • Proton
  • Proton EBRT
  • Proton External Beam Radiotherapy
  • Radiation, Proton Beam
  • PROTON Therapy
  • External beam radiation therapy protons (procedure)
  • External Beam Radiotherapy (protons)
Drug: Docetaxel
IV
Other Names:
  • Taxotere
  • Docecad
  • RP56976
  • Taxotere Injection Concentrate
  • RP 56976
  • RP-56976
Drug: Capecitabine
Oral
Other Names:
  • Xeloda
  • Ro 09-1978/000
Drug: Leucovorin Calcium
Oral
Other Names:
  • Wellcovorin
  • folinic acid
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
Active Comparator: 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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • JM8
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol Konzentrat
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Fluorouracil
IV
Other Names:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Drug: Oxaliplatin
IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • Ai Heng
  • Aiheng
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669
  • SR96669
  • Elplat
  • JM 83
  • JM83
  • RP54780
  • SR 96669
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Esophagectomy
Undergo esophagectomy
Other Names:
  • excision of the esophagus
Drug: Docetaxel
IV
Other Names:
  • Taxotere
  • Docecad
  • RP56976
  • Taxotere Injection Concentrate
  • RP 56976
  • RP-56976
Drug: Capecitabine
Oral
Other Names:
  • Xeloda
  • Ro 09-1978/000
Drug: Leucovorin Calcium
Oral
Other Names:
  • Wellcovorin
  • folinic acid
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 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
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
Time Frame: From baseline up to 8 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic response rate
Time Frame: At time of surgery
A Chi-square test will be used to compare the pathologic response rates between the treatment arms.
At time of surgery
Distant metastatic-free survival (DMFS)
Time Frame: From the date of randomization to the date of first DMFS failure or last follow-up for patients without a reported DMFS event, assessed up to 8 years
Will be defined as appearance of distant metastasis or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with DMFS.
From the date of randomization to the date of first DMFS failure or last follow-up for patients without a reported DMFS event, assessed up to 8 years
Progression-free survival
Time Frame: From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 8 years
Will be defined as appearance of local/regional/distant failure or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS.
From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 8 years
Quality-adjusted life years (QALY)
Time Frame: Assessed up to 8 years
Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met.
Assessed up to 8 years
Cost-benefit economic analysis of treatment
Time Frame: Assessed up to 8 years
Will be calculated by the visual analog scale (VAS) and index scores form the EQ-5D-5L only be done if primary endpoint is met. Will be compared between treatment arms using a t-test with a 2-sided significance level of 0.05. If there are significant differences, then a cost analysis will be conducted.
Assessed up to 8 years
Change in patient reported outcomes (PROs) of symptom and function
Time Frame: Baseline up to 12 months after end of chemoradiation
Will be assessed using the MD Anderson Symptom Inventory (MDASI) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue tools. The primary analysis cohorts for PRO endpoints will be intent-to-treat, with sensitivity analyses done limited to patients that started protocol treatment. General linear models with maximum likelihood estimation will be used to assess MDASI symptom severity and functioning trends across time as the primary PRO endpoints. Mean change (follow-up time point - baseline score) in fatigue will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead. Additionally, a general linear model with maximum likelihood estimation will be used to assess fatigue trends across time.
Baseline up to 12 months after end of chemoradiation
Length of hospitalization
Time Frame: From baseline up to 8 years
Will be defined as number of days in the hospital post protocol-defined surgery. Mean hospitalization days will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
From baseline up to 8 years
Grade 4 lymphopenia during chemoradiation
Time Frame: From baseline up to 8 years
Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients experiencing grade 4 lymphopenia during chemoradiation will be compared between treatment arms using a chi-squared test.
From baseline up to 8 years
Lymphocyte counts
Time Frame: From baseline up to 8 years
Mean lymphocyte counts at first post chemoradiation follow-up will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
From baseline up to 8 years
Locoregional failure (LRF)
Time Frame: From the date of randomization to the date of first LRF or date of last follow-up for patients without an LRF event reported, assessed up to 8 years
Will be defined as local/regional recurrence or progression. Will be estimated by the cumulative incidence method, with death as a competing risk. The distribution of LRF estimates between the two arms will be compared using Gray's test. The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LRF.
From the date of randomization to the date of first LRF or date of last follow-up for patients without an LRF event reported, assessed up to 8 years

Collaborators and Investigators

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

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven H Lin, NRG Oncology

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)

June 26, 2019

Primary Completion (Estimated)

November 7, 2031

Study Completion (Estimated)

November 7, 2036

Study Registration Dates

First Submitted

January 3, 2019

First Submitted That Met QC Criteria

January 9, 2019

First Posted (Actual)

January 14, 2019

Study Record Updates

Last Update Posted (Actual)

August 24, 2026

Last Update Submitted That Met QC Criteria

August 20, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-GI006 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2018-03378 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180822 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

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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