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Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

Trial Status: Active

This trial studies how well proton beam radiation therapy compared with intensity modulated photo 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 photo radiotherapy will work better in treating patients with esophageal cancer.

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
  • 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)
  • Creatinine clearance > 50 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 * Symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia not controlled by pacer device 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

Arizona

Phoenix
Mayo Clinic Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015
Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015

Florida

Miami
Miami Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 786-596-2000

Georgia

Atlanta
Emory Proton Therapy Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-251-2854
Emory Saint Joseph's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-851-7115
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-778-1868
Emory University Hospital Midtown
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-946-7447

Illinois

DeKalb
Northwestern Medicine Cancer Center Kishwaukee
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-315-1918
Geneva
Northwestern Medicine Cancer Center Delnor
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-315-1918
Warrenville
Northwestern Medicine Cancer Center Warrenville
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-315-1918

Maryland

Baltimore
Maryland Proton Treatment Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 410-369-5226
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-888-8823

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-726-5130

Michigan

Dearborn
Beaumont Hospital - Dearborn
Status: ACTIVE
Contact: Site Public Contact
Phone: 248-551-7695
Royal Oak
William Beaumont Hospital-Royal Oak
Status: ACTIVE
Contact: Site Public Contact
Phone: 248-551-7695
Troy
William Beaumont Hospital - Troy
Status: ACTIVE
Contact: Site Public Contact
Phone: 248-551-7695

Minnesota

Albert Lea
Mayo Clinic Health System in Albert Lea
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015
Mankato
Mayo Clinic Health Systems-Mankato
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015
Maplewood
Minnesota Oncology Hematology PA-Maplewood
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Northfield
Mayo Clinic Radiation Therapy-Northfield
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015
Rochester
Mayo Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015

Ohio

Beachwood
UHHS-Chagrin Highlands Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Chardon
Geauga Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Cincinnati
University of Cincinnati / Barrett Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 513-558-4553
Cleveland
Case Western Reserve University
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Elyria
Mercy Cancer Center-Elyria
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Mayfield Heights
UH Seidman Cancer Center at Landerbrook Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Mentor
UH Seidman Cancer Center at Lake Health Mentor Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Middleburg Heights
UH Seidman Cancer Center at Southwest General Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Parma
University Hospitals Parma Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Ravenna
University Hospitals Portage Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Sandusky
UH Seidman Cancer Center at Firelands Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
Wadsworth
University Hospitals Sharon Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
West Chester
University Pointe
Status: ACTIVE
Contact: Site Public Contact
Westlake
UH Seidman Cancer Center at Saint John Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422
UHHS-Westlake Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-641-2422

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-271-8777

Texas

Conroe
MD Anderson in The Woodlands
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-632-6789
Houston
M D Anderson Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-632-6789
MD Anderson West Houston
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-632-6789
Sugar Land
MD Anderson in Sugar Land
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-632-6789

Washington

Seattle
University of Washington Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-8824

Wisconsin

Eau Claire
Mayo Clinic Health System-Eau Claire Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 855-776-0015

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.

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.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
NRG Oncology

Principal Investigator
Steven H. Lin

  • Primary ID NRG-GI006
  • Secondary IDs NCI-2018-03378
  • Clinicaltrials.gov ID NCT03801876