Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

February 5, 2024 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

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 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.

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
        • Recruiting
        • Mayo Clinic Hospital in Arizona
        • Principal Investigator:
          • Christopher L. Hallemeier
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
      • Scottsdale, Arizona, United States, 85259
        • Active, not recruiting
        • Mayo Clinic in Arizona
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • William Jin
      • Deerfield Beach, Florida, United States, 33442
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • William Jin
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • William Jin
      • Miami, Florida, United States, 33176
        • Recruiting
        • Miami Cancer Institute
        • Principal Investigator:
          • Michael D. Chuong
        • Contact:
          • Site Public Contact
          • Phone Number: 786-596-2000
      • Orlando, Florida, United States, 32806
        • Active, not recruiting
        • Orlando Health Cancer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Active, not recruiting
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Active, not recruiting
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Active, not recruiting
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30308
        • Active, not recruiting
        • Emory Proton Therapy Center
    • Illinois
      • Alton, Illinois, United States, 62002
        • Recruiting
        • Alton Memorial Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 618-463-7323
        • Principal Investigator:
          • Gregory R. Vlacich
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Principal Investigator:
          • Stephen A. Mihalcik
        • Contact:
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Principal Investigator:
          • Stephen A. Mihalcik
        • Contact:
      • Shiloh, Illinois, United States, 62269
        • Recruiting
        • Memorial Hospital East
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Principal Investigator:
          • Stephen A. Mihalcik
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Jason K. Molitoris
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • Maryland Proton Treatment Center
        • Contact:
        • Principal Investigator:
          • Jason K. Molitoris
      • Bel Air, Maryland, United States, 21014
        • Recruiting
        • UM Upper Chesapeake Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 443-643-3010
        • Principal Investigator:
          • Jack J. Hong
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Principal Investigator:
          • Florence K. Keane
        • Contact:
          • Site Public Contact
          • Phone Number: 877-726-5130
    • Michigan
      • Bay City, Michigan, United States, 48706
        • Recruiting
        • McLaren Cancer Institute-Bay City
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Dearborn, Michigan, United States, 48124
        • Recruiting
        • Beaumont Hospital - Dearborn
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Weisberg Cancer Treatment Center
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Flint, Michigan, United States, 48532
        • Recruiting
        • McLaren Cancer Institute-Flint
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Lansing, Michigan, United States, 48910
        • Recruiting
        • Karmanos Cancer Institute at McLaren Greater Lansing
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Lapeer, Michigan, United States, 48446
        • Recruiting
        • McLaren Cancer Institute-Lapeer Region
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Owosso, Michigan, United States, 48867
        • Recruiting
        • McLaren Cancer Institute-Owosso
        • Principal Investigator:
          • Christian C. Hyde
        • Contact:
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • William Beaumont Hospital-Royal Oak
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Troy, Michigan, United States, 48085
        • Recruiting
        • William Beaumont Hospital - Troy
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
    • Minnesota
      • Albert Lea, Minnesota, United States, 56007
        • Completed
        • Mayo Clinic Health System in Albert Lea
      • Coon Rapids, Minnesota, United States, 55433
        • Recruiting
        • Mercy Hospital
        • Contact:
        • Principal Investigator:
          • Charles Shideman
      • Fridley, Minnesota, United States, 55432
        • Active, not recruiting
        • Unity Hospital
      • Mankato, Minnesota, United States, 56001
        • Completed
        • Mayo Clinic Health Systems-Mankato
      • Maplewood, Minnesota, United States, 55109
        • Recruiting
        • Minnesota Oncology Hematology PA-Maplewood
        • Contact:
        • Principal Investigator:
          • Charles Shideman
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center
        • Contact:
        • Principal Investigator:
          • Charles Shideman
      • Northfield, Minnesota, United States, 55057
        • Recruiting
        • Mayo Clinic Radiation Therapy-Northfield
        • Principal Investigator:
          • Christopher L. Hallemeier
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Christopher L. Hallemeier
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
    • Missouri
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
      • Saint Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
      • Saint Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
      • Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Contact:
        • Principal Investigator:
          • Gregory R. Vlacich
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
      • New York, New York, United States, 10035
        • Recruiting
        • New York Proton Center
        • Contact:
        • Principal Investigator:
          • Jehee I. Choi
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Abraham J. Wu
    • Ohio
      • Avon, Ohio, United States, 44011
        • Recruiting
        • UH Seidman Cancer Center at UH Avon Health Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
          • Site Public Contact
          • Phone Number: 800-641-2422
      • Beachwood, Ohio, United States, 44122
        • Recruiting
        • UHHS-Chagrin Highlands Medical Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Chardon, Ohio, United States, 44024
        • Recruiting
        • Geauga Hospital
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Jordan Kharofa
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case Western Reserve University
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Elyria, Ohio, United States, 44035
        • Suspended
        • Mercy Cancer Center-Elyria
      • Mayfield Heights, Ohio, United States, 44124
        • Recruiting
        • UH Seidman Cancer Center at Landerbrook Health Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Mentor, Ohio, United States, 44060
        • Recruiting
        • UH Seidman Cancer Center at Lake Health Mentor Campus
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Middleburg Heights, Ohio, United States, 44130
        • Recruiting
        • UH Seidman Cancer Center at Southwest General Hospital
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Parma, Ohio, United States, 44129
        • Recruiting
        • University Hospitals Parma Medical Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Ravenna, Ohio, United States, 44266
        • Recruiting
        • University Hospitals Portage Medical Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Sandusky, Ohio, United States, 44870
        • Recruiting
        • UH Seidman Cancer Center at Firelands Regional Medical Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • Wadsworth, Ohio, United States, 44281
        • Recruiting
        • University Hospitals Sharon Health Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • West Chester, Ohio, United States, 45069
        • Recruiting
        • University of Cincinnati Cancer Center-West Chester
        • Principal Investigator:
          • Jordan Kharofa
        • Contact:
      • Westlake, Ohio, United States, 44145
        • Suspended
        • UH Seidman Cancer Center at Saint John Medical Center
      • Westlake, Ohio, United States, 44145
        • Recruiting
        • UHHS-Westlake Medical Center
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Tyler Gunter
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania/Abramson Cancer Center
        • Principal Investigator:
          • John P. Plastaras
        • Contact:
          • Site Public Contact
          • Phone Number: 800-474-9892
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Recruiting
        • Thompson Cancer Survival Center
        • Contact:
          • Site Public Contact
          • Phone Number: 865-331-1812
        • Principal Investigator:
          • Grant M. Clark
      • Knoxville, Tennessee, United States, 37932
        • Recruiting
        • Thompson Cancer Survival Center - West
        • Contact:
          • Site Public Contact
          • Phone Number: 865-331-1812
        • Principal Investigator:
          • Grant M. Clark
      • Knoxville, Tennessee, United States, 37909
        • Recruiting
        • Thompson Proton Center
        • Contact:
        • Principal Investigator:
          • Grant M. Clark
      • Maryville, Tennessee, United States, 37804
        • Recruiting
        • Thompson Oncology Group-Maryville
        • Contact:
          • Site Public Contact
          • Phone Number: 865-331-1812
        • Principal Investigator:
          • Grant M. Clark
      • Oak Ridge, Tennessee, United States, 37830
        • Recruiting
        • Thompson Oncology Group-Oak Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 865-331-1812
        • Principal Investigator:
          • Grant M. Clark
    • Texas
      • Conroe, Texas, United States, 77384
        • Recruiting
        • MD Anderson in The Woodlands
        • Contact:
        • Principal Investigator:
          • Saumil Gandhi
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Saumil Gandhi
      • Houston, Texas, United States, 77079
        • Recruiting
        • MD Anderson West Houston
        • Contact:
        • Principal Investigator:
          • Saumil Gandhi
      • League City, Texas, United States, 77573
        • Recruiting
        • MD Anderson League City
        • Contact:
        • Principal Investigator:
          • Saumil Gandhi
      • Sugar Land, Texas, United States, 77478
        • Recruiting
        • MD Anderson in Sugar Land
        • Contact:
        • Principal Investigator:
          • Saumil Gandhi
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Shane Lloyd
    • Virginia
      • Alexandria, Virginia, United States, 22304
        • Recruiting
        • Inova Alexandria Hospital
        • Contact:
        • Principal Investigator:
          • Avani D. Rao
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Principal Investigator:
          • Avani D. Rao
        • Contact:
      • Fairfax, Virginia, United States, 22033
        • Recruiting
        • Inova Fair Oaks Hospital
        • Principal Investigator:
          • Avani D. Rao
        • Contact:
      • Leesburg, Virginia, United States, 20176
        • Recruiting
        • Inova Loudoun Hospital
        • Principal Investigator:
          • Avani D. Rao
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98195
        • Active, not recruiting
        • University of Washington Medical Center - Montlake
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Recruiting
        • Mayo Clinic Health System-Eau Claire Clinic
        • Principal Investigator:
          • Christopher L. Hallemeier
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015

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 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 >= 1,500 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, Chemotherapy, Esophagectomy)
Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
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
Drug: Docetaxel
Chemotherapy
Other Names:
  • Taxotere
Procedure: Esophagectomy
Undergo esophagectomy
Other Names:
  • excision of the esophagus
Radiation: Proton Beam Radiation Therapy
Undergo PBT
Other Names:
  • Proton Radiation Therapy
  • PBRT
Drug: FOLFOX regimen
Folinic acid, flurouracil and oxaliplatin
Other Names:
  • FOLFOX
Drug: CAPOX regimen
Capecitabine combined with oxaliplatin
Other Names:
  • CAPE-OX
  • OxCap
Drug: 5FU
Chemotherapy
Other Names:
  • 5-FU
  • Carac
  • Adrucil
  • Efudex
  • Fluoroplex
  • Tolak
  • flurouracil
Active Comparator: Group II (IMRT, Chemotherapy, Esophagectomy)
Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
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
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Drug: Docetaxel
Chemotherapy
Other Names:
  • Taxotere
Procedure: Esophagectomy
Undergo esophagectomy
Other Names:
  • excision of the esophagus
Drug: FOLFOX regimen
Folinic acid, flurouracil and oxaliplatin
Other Names:
  • FOLFOX
Drug: CAPOX regimen
Capecitabine combined with oxaliplatin
Other Names:
  • CAPE-OX
  • OxCap
Drug: 5FU
Chemotherapy
Other Names:
  • 5-FU
  • Carac
  • Adrucil
  • Efudex
  • Fluoroplex
  • Tolak
  • flurouracil

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
Grade 4 lymphopenia during chemoradiation
Time Frame: From the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days
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 the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days
Lymphocyte counts
Time Frame: From the last date of chemoradiation up to 8 weeks post chemoradiation
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 the last date of chemoradiation up to 8 weeks post chemoradiation
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
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

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 Lin, NRG Oncology

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)

March 15, 2019

Primary Completion (Estimated)

December 21, 2026

Study Completion (Estimated)

December 21, 2031

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)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

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)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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