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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer

Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer (NCT03801876) is a Phase 3 interventional studying Clinical Stage I Esophageal Adenocarcinoma AJCC v8 and Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8, sponsored by NRG Oncology. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Clinical Stage I Esophageal Adenocarcinoma AJCC v8, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 300 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: - 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: white blood cell count (ANC) at least 1,500 cells/mm\^3 - For patients who DID receive induction chemotherapy: white blood cell count (ANC) at least 1,000 cells/mm\^3 - Platelets (within 30 days prior to Step 1 registration) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

DRUG

Capecitabine

Oral

DRUG

Carboplatin

Given IV

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

DRUG

Docetaxel

IV

PROCEDURE

Esophagectomy

Undergo esophagectomy

DRUG

Fluorouracil

IV

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

DRUG

Leucovorin Calcium

Oral

DRUG

Oxaliplatin

IV

DRUG

Paclitaxel

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

RADIATION

Proton Beam Radiation Therapy

Undergo PBT

OTHER

Quality-of-Life Assessment

Ancillary studies

OTHER

Questionnaire Administration

Ancillary studies

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Miami Cancer Institute
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Emory Proton Therapy Center
Atlanta, Georgia, United States
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Alton Memorial Hospital
Alton, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Memorial Hospital East
Shiloh, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03801876), the sponsor (NRG Oncology), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03801876 clinical trial studying?

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 radiother… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03801876?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03801876?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03801876. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03801876. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.