Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

This study is comparing two types of radiation therapy for esophageal cancer: proton beam radiation therapy and intensity modulated photon radiotherapy. Proton therapy uses a beam of protons, while photon radiotherapy uses high-energy X-rays, both aiming to target the tumor while sparing healthy tissue. Researchers want to see if proton therapy improves overall survival and causes fewer serious heart and lung side effects compared to photon therapy. You may be eligible if you have Stage I-IVA esophageal adenocarcinoma or squamous cell carcinoma. The study is also looking at how treatments affect your quality of life and symptoms. The current recruitment status is unclear.

Study design: This interventional study plans to enroll 300 participants. It compares proton beam radiation therapy with intensity modulated photon radiotherapy.
What's involved: Participants will undergo blood sample collection, CT or PET/CT scans, and receive either Capecitabine, Carboplatin, or Docetaxel, along with one of the radiation therapies.
Compensation: Not stated in the trial record.
Follow-up: Overall survival will be measured until death or last follow-up, estimated to be 4 years after enrollment is complete. Adverse events will be monitored for up to 8 years.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

Active, Not Recruiting

PHASE3Ages 18+InterventionalTreatment

NRG Oncology

~300 participants

Updated 2026-08-24 on ClinicalTrials.gov

What's tested:Biospecimen CollectionCapecitabineCarboplatinComputed TomographyDocetaxelEsophagectomy

At a glance

Recruiting sites

0 of 96 listed sites are recruiting right now

RecruitingSuspended, closed, or not yet open

What they're measuring

Overall survival (OS)

Measured over 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

+1 more outcome measured

Conditions

Clinical Stage I Esophageal Adenocarcinoma AJCC v8

Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8

Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage II Esophageal Adenocarcinoma AJCC v8

Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8

Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage III Esophageal Adenocarcinoma AJCC v8

Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8

Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8

Clinical Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8

Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8

Thoracic Esophagus Squamous Cell Carcinoma

NCT03801876

Where you'd take part

This study runs at 96 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

Alton Memorial Hospital
Alton, Illinoisno site contact published
Case Western Reserve University
Cleveland, Ohiono site contact published
Corewell Health Beaumont Troy Hospital
Troy, Michiganno site contact published
Corewell Health Dearborn Hospital
Dearborn, Michiganno site contact published
Corewell Health William Beaumont University Hospital
Royal Oak, Michiganno site contact published
Covenant Health Cancer Centers
Knoxville, Tennesseeno site contact published
Covenant Health Cancer Centers - West
Knoxville, Tennesseeno site contact published
Covenant Health Oncology Group - Maryville
Maryville, Tennesseeno site contact published

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

Steven H Lin · PRINCIPAL_INVESTIGATOR · NRG Oncology

Who to contact

This trial hasn't published a contact. View it on ClinicalTrials.gov

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Eligibility criteria

Inclusion

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

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

What this trial measures

Overall survival (OS)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.
Incidence of specific grade 3+ cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatmentFrom 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.

Trialytics