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Comparing two types of 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

Phase 3 Interventional NRG Oncology · NCT03801876

This study is testing whether proton beam radiation therapy is better than traditional photon radiation therapy for helping people with stage I-IVA esophageal cancer live longer and have fewer side effects.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment300 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionsdurvalumab, chemotherapy, radiation
Locations95 sites (Phoenix, Arizona and 94 other locations)
Trial IDNCT03801876 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of proton beam radiation therapy (PBT) versus intensity-modulated photon radiation therapy (IMRT) in treating patients with stage I-IVA esophageal cancer. The study aims to determine if PBT improves overall survival and reduces severe cardiopulmonary toxicity compared to IMRT. Secondary objectives include assessing symptom burden, quality of life, pathologic response rates, and economic analysis of the two treatment modalities. Patients will be monitored for various health outcomes and side effects throughout the treatment process.

Who should consider this trial

Good fit: Ideal candidates include individuals with histologically confirmed stage I-IVA esophageal adenocarcinoma or squamous cell carcinoma.

Not a fit: Patients with T4b stage esophageal cancer or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates and reduced side effects for patients with esophageal cancer.

How similar studies have performed: Other studies have shown promising results with proton therapy in various cancers, suggesting potential benefits in this novel application for esophageal cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Phoenix, Arizona and 94 other locations

+45 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
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 v8
Last reviewed 2026-06-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.