Back to Trials
NCT03801876PHASE3Recruiting

Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

NRG Oncology

Start Date

6/26/2019

Completion Date

12/21/2031

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

PROCEDURE

Biospecimen Collection

DRUG

Capecitabine

DRUG

Carboplatin

PROCEDURE

Computed Tomography

DRUG

Docetaxel

PROCEDURE

Esophagectomy

DRUG

Fluorouracil

RADIATION

Intensity-Modulated Radiation Therapy

DRUG

Leucovorin Calcium

DRUG

Oxaliplatin

DRUG

Paclitaxel

PROCEDURE

Positron Emission Tomography

RADIATION

Proton Beam Radiation Therapy

OTHER

Quality-of-Life Assessment

OTHER

Questionnaire Administration

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Clinical Stage I Esophageal Adenocarcinoma AJCC v8Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage II Esophageal Adenocarcinoma AJCC v8Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage III Esophageal Adenocarcinoma AJCC v8Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8Clinical Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Thoracic Esophagus Squamous Cell Carcinoma

Locations

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

Mayo Clinic in Arizona

Scottsdale, Arizona 85259

United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas 72205

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida 33442

United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida 33166

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida 33136

United States

Miami Cancer Institute

Miami, Florida 33176

United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida 33176

United States

Orlando Health Cancer Institute

Orlando, Florida 32806

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida 33324

United States

Emory Proton Therapy Center

Atlanta, Georgia 30308

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

United States

Alton Memorial Hospital

Alton, Illinois 62002

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

Memorial Hospital East

Shiloh, Illinois 62269

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

Maryland Proton Treatment Center

Baltimore, Maryland 21201

United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland 21201

United States

UM Upper Chesapeake Medical Center

Bel Air, Maryland 21014

United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts 02114

United States

McLaren Cancer Institute-Bay City

Bay City, Michigan 48706

United States

Corewell Health Dearborn Hospital

Dearborn, Michigan 48124

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan 48334

United States

McLaren Cancer Institute-Flint

Flint, Michigan 48532

United States

Karmanos Cancer Institute at McLaren Greater Lansing

Lansing, Michigan 48910

United States

McLaren Cancer Institute-Lapeer Region

Lapeer, Michigan 48446

United States

McLaren Cancer Institute-Central Michigan

Mount Pleasant, Michigan 48858

United States

McLaren Cancer Institute-Owosso

Owosso, Michigan 48867

United States

Corewell Health William Beaumont University Hospital

Royal Oak, Michigan 48073

United States

Corewell Health Beaumont Troy Hospital

Troy, Michigan 48085

United States

Mayo Clinic Health System in Albert Lea

Albert Lea, Minnesota 56007

United States

Mercy Hospital

Coon Rapids, Minnesota 55433

United States

Unity Hospital

Fridley, Minnesota 55432

United States

Mayo Clinic Health Systems-Mankato

Mankato, Minnesota 56001

United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota 55109

United States

Hennepin County Medical Center

Minneapolis, Minnesota 55415

United States

Mayo Clinic Radiation Therapy-Northfield

Northfield, Minnesota 55057

United States

Mayo Clinic in Rochester

Rochester, Minnesota 55905

United States

Ridgeview Medical Center

Waconia, Minnesota 55387

United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri 63376

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri 63141

United States

Mercy Hospital Springfield

Springfield, Missouri 65804

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Mercy Hospital South

St Louis, Missouri 63128

United States

Siteman Cancer Center-South County

St Louis, Missouri 63129

United States

Siteman Cancer Center at Christian Hospital

St Louis, Missouri 63136

United States

Mercy Hospital Saint Louis

St Louis, Missouri 63141

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey 07920

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey 07645

United States

Memorial Sloan Kettering Commack

Commack, New York 11725

United States

Memorial Sloan Kettering Westchester

Harrison, New York 10604

United States

New York Proton Center

New York, New York 10035

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Memorial Sloan Kettering Nassau

Uniondale, New York 11553

United States

UH Seidman Cancer Center at UH Avon Health Center

Avon, Ohio 44011

United States

UHHS-Chagrin Highlands Medical Center

Beachwood, Ohio 44122

United States

Geauga Hospital

Chardon, Ohio 44024

United States

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio 45219

United States

Case Western Reserve University

Cleveland, Ohio 44106

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Mercy Cancer Center-Elyria

Elyria, Ohio 44035

United States

UH Seidman Cancer Center at Landerbrook Health Center

Mayfield Heights, Ohio 44124

United States

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio 44060

United States

UH Seidman Cancer Center at Southwest General Hospital

Middleburg Heights, Ohio 44130

United States

University Hospitals Parma Medical Center

Parma, Ohio 44129

United States

University Hospitals Portage Medical Center

Ravenna, Ohio 44266

United States

UH Seidman Cancer Center at Firelands Regional Medical Center

Sandusky, Ohio 44870

United States

University Hospitals Sharon Health Center

Wadsworth, Ohio 44281

United States

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio 45069

United States

UH Seidman Cancer Center at Saint John Medical Center

Westlake, Ohio 44145

United States

UHHS-Westlake Medical Center

Westlake, Ohio 44145

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

Covenant Health Proton Center

Knoxville, Tennessee 37909

United States

Covenant Health Cancer Centers

Knoxville, Tennessee 37916

United States

Covenant Health Cancer Centers - West

Knoxville, Tennessee 37932

United States

Covenant Health Oncology Group - Maryville

Maryville, Tennessee 37804

United States

Covenant Health Oncology Group - Oak Ridge

Oak Ridge, Tennessee 37830

United States

MD Anderson in The Woodlands

Conroe, Texas 77384

United States

UT MD Anderson Cancer Center

Houston, Texas 77030

United States

MD Anderson West Houston

Houston, Texas 77079

United States

UT MD Anderson - League City

League City, Texas 77573

United States

MD Anderson in Sugar Land

Sugar Land, Texas 77478

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah 84112

United States

Inova Alexandria Hospital

Alexandria, Virginia 22304

United States

Inova Schar Cancer Institute

Fairfax, Virginia 22031

United States

Inova Fair Oaks Hospital

Fairfax, Virginia 22033

United States

Inova Loudoun Hospital

Leesburg, Virginia 20176

United States

University of Washington Medical Center - Montlake

Seattle, Washington 98195

United States

Mayo Clinic Health System-Eau Claire Clinic

Eau Claire, Wisconsin 54701

United States