Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

Last updated: January 21, 2025
Sponsor: NRG Oncology
Overall Status: Active - Recruiting

Phase

3

Condition

Adenocarcinoma

Esophageal Disorders

Squamous Cell Carcinoma

Treatment

Proton Beam Radiation Therapy

Quality-of-Life Assessment

CAPOX regimen

Clinical Study ID

NCT03801876
NRG-GI006
U10CA180822
U10CA180868
NRG-GI006
NCI-2018-03378
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:

  • Histologically proven diagnosis of adenocarcinoma or squamous cell carcinoma of thethoracic 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) orchest/abdominal (include pelvic if clinically indicated) CT with contrast

  • For patients who DID NOT receive induction chemotherapy, scan must occurwithin 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 adiagnosis of AJCC stage I-IVA, excluding T4b, esophageal cancer areeligible

  • Surgical consultation to determine whether or not the patient is a candidate forresection after completion of chemoradiation

  • Induction chemotherapy for the current malignancy prior to concurrent chemoradiationallowed if last dose is no more than 90 days and no less than 10 days prior to Step 1 registration. Only FOLFOX will be allowed as the induction chemotherapy regimen.

  • 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 >= 1,500cells/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 toachieve 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 > 40mL/min estimated by Cockcroft-Gault formula (within 30 days prior to Step 1registration)

  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days prior to Step 1registration)

  • 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 registrationfor women of child bearing potential

  • The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry

Exclusion

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 courseof 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 1registration

  • Uncontrolled symptomatic congestive heart failure, unstable angina, or cardiacarrhythmia not controlled by any device or medication at the time of Step 1registration

  • 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 undertreatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note also that HIVtesting is not required for eligibility for this protocol. This exclusion criterionis necessary because the treatments involved in this protocol may be significantlyimmunosuppressive

  • PRIOR TO STEP 2 REGISTRATION:

  • Unable to obtain confirmation of payment coverage (insurance or other) for eitherpossible radiation treatment

Study Design

Total Participants: 300
Treatment Group(s): 11
Primary Treatment: Proton Beam Radiation Therapy
Phase: 3
Study Start date:
March 15, 2019
Estimated Completion Date:
December 21, 2031

Study 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 paclitaxel intravenously (IV) and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT.

GROUP II: Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT.

In both groups, within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.

After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually thereafter.

Connect with a study center

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona 85054
    United States

    Active - Recruiting

  • Mayo Clinic in Arizona

    Scottsdale, Arizona 85259
    United States

    Site Not Available

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas 72205
    United States

    Active - Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida 33146
    United States

    Active - Recruiting

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida 33442
    United States

    Active - Recruiting

  • Miami Cancer Institute

    Miami, Florida 33176
    United States

    Active - Recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida 33136
    United States

    Active - Recruiting

  • Orlando Health Cancer Institute

    Orlando, Florida 32806
    United States

    Site Not Available

  • Emory Proton Therapy Center

    Atlanta, Georgia 30308
    United States

    Site Not Available

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia 30342
    United States

    Site Not Available

  • Emory University Hospital Midtown

    Atlanta, Georgia 30308
    United States

    Site Not Available

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Alton Memorial Hospital

    Alton, Illinois 62002
    United States

    Active - Recruiting

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois 60115
    United States

    Active - Recruiting

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois 60134
    United States

    Active - Recruiting

  • Memorial Hospital East

    Shiloh, Illinois 62269
    United States

    Active - Recruiting

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois 60555
    United States

    Active - Recruiting

  • Maryland Proton Treatment Center

    Baltimore, Maryland 21201
    United States

    Active - Recruiting

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland 21201
    United States

    Active - Recruiting

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland 21014
    United States

    Active - Recruiting

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan 48706
    United States

    Active - Recruiting

  • Beaumont Hospital - Dearborn

    Dearborn, Michigan 48124
    United States

    Active - Recruiting

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan 48124
    United States

    Active - Recruiting

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan 48201
    United States

    Active - Recruiting

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan 48334
    United States

    Active - Recruiting

  • McLaren Cancer Institute-Flint

    Flint, Michigan 48532
    United States

    Active - Recruiting

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan 48910
    United States

    Active - Recruiting

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan 48446
    United States

    Active - Recruiting

  • McLaren Cancer Institute-Owosso

    Owosso, Michigan 48867
    United States

    Active - Recruiting

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan 48073
    United States

    Active - Recruiting

  • William Beaumont Hospital-Royal Oak

    Royal Oak, Michigan 48073
    United States

    Active - Recruiting

  • Corewell Health Beaumont Troy Hospital

    Troy, Michigan 48085
    United States

    Active - Recruiting

  • William Beaumont Hospital - Troy

    Troy, Michigan 48085
    United States

    Active - Recruiting

  • Mayo Clinic Health System in Albert Lea

    Albert Lea, Minnesota 56007
    United States

    Completed

  • Mercy Hospital

    Coon Rapids, Minnesota 55433
    United States

    Active - Recruiting

  • Unity Hospital

    Fridley, Minnesota 55432
    United States

    Site Not Available

  • Mayo Clinic Health Systems-Mankato

    Mankato, Minnesota 56001
    United States

    Completed

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota 55109
    United States

    Active - Recruiting

  • Hennepin County Medical Center

    Minneapolis, Minnesota 55415
    United States

    Active - Recruiting

  • Mayo Clinic Radiation Therapy-Northfield

    Northfield, Minnesota 55057
    United States

    Active - Recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • Ridgeview Medical Center

    Waconia, Minnesota 55387
    United States

    Active - Recruiting

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri 63141
    United States

    Active - Recruiting

  • Mercy Hospital Saint Louis

    Saint Louis, Missouri 63141
    United States

    Active - Recruiting

  • Siteman Cancer Center at Christian Hospital

    Saint Louis, Missouri 63136
    United States

    Active - Recruiting

  • Siteman Cancer Center-South County

    Saint Louis, Missouri 63129
    United States

    Active - Recruiting

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Siteman Cancer Center at Saint Peters Hospital

    Saint Peters, Missouri 63376
    United States

    Active - Recruiting

  • Mercy Hospital Springfield

    Springfield, Missouri 65804
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey 07920
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey 07748
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey 07645
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Commack

    Commack, New York 11725
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Westchester

    Harrison, New York 10604
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Active - Recruiting

  • New York Proton Center

    New York, New York 10035
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Nassau

    Uniondale, New York 11553
    United States

    Active - Recruiting

  • UH Seidman Cancer Center at UH Avon Health Center

    Avon, Ohio 44011
    United States

    Active - Recruiting

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio 44122
    United States

    Active - Recruiting

  • Geauga Hospital

    Chardon, Ohio 44024
    United States

    Active - Recruiting

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio 45219
    United States

    Active - Recruiting

  • Case Western Reserve University

    Cleveland, Ohio 44106
    United States

    Active - Recruiting

  • Mercy Cancer Center-Elyria

    Elyria, Ohio 44035
    United States

    Suspended

  • UH Seidman Cancer Center at Landerbrook Health Center

    Mayfield Heights, Ohio 44124
    United States

    Active - Recruiting

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio 44060
    United States

    Active - Recruiting

  • UH Seidman Cancer Center at Southwest General Hospital

    Middleburg Heights, Ohio 44130
    United States

    Active - Recruiting

  • University Hospitals Parma Medical Center

    Parma, Ohio 44129
    United States

    Active - Recruiting

  • University Hospitals Portage Medical Center

    Ravenna, Ohio 44266
    United States

    Active - Recruiting

  • UH Seidman Cancer Center at Firelands Regional Medical Center

    Sandusky, Ohio 44870
    United States

    Active - Recruiting

  • University Hospitals Sharon Health Center

    Wadsworth, Ohio 44281
    United States

    Active - Recruiting

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio 45069
    United States

    Active - Recruiting

  • UH Seidman Cancer Center at Saint John Medical Center

    Westlake, Ohio 44145
    United States

    Suspended

  • UHHS-Westlake Medical Center

    Westlake, Ohio 44145
    United States

    Active - Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma 73104
    United States

    Active - Recruiting

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Thompson Cancer Survival Center

    Knoxville, Tennessee 37916
    United States

    Active - Recruiting

  • Thompson Cancer Survival Center - West

    Knoxville, Tennessee 37932
    United States

    Active - Recruiting

  • Thompson Proton Center

    Knoxville, Tennessee 37909
    United States

    Active - Recruiting

  • Thompson Oncology Group-Maryville

    Maryville, Tennessee 37804
    United States

    Suspended

  • Thompson Oncology Group-Oak Ridge

    Oak Ridge, Tennessee 37830
    United States

    Active - Recruiting

  • MD Anderson in The Woodlands

    Conroe, Texas 77384
    United States

    Active - Recruiting

  • M D Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • MD Anderson West Houston

    Houston, Texas 77079
    United States

    Active - Recruiting

  • MD Anderson League City

    League City, Texas 77573
    United States

    Active - Recruiting

  • MD Anderson in Sugar Land

    Sugar Land, Texas 77478
    United States

    Active - Recruiting

  • MD Anderson in The Woodlands

    The Woodlands, Texas 77384
    United States

    Site Not Available

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah 84112
    United States

    Active - Recruiting

  • Inova Alexandria Hospital

    Alexandria, Virginia 22304
    United States

    Site Not Available

  • Inova Fair Oaks Hospital

    Fairfax, Virginia 22033
    United States

    Site Not Available

  • Inova Schar Cancer Institute

    Fairfax, Virginia 22031
    United States

    Site Not Available

  • Inova Loudoun Hospital

    Leesburg, Virginia 20176
    United States

    Site Not Available

  • University of Washington Medical Center - Montlake

    Seattle, Washington 98195
    United States

    Site Not Available

  • Mayo Clinic Health System-Eau Claire Clinic

    Eau Claire, Wisconsin 54701
    United States

    Completed

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.