Clinical Stage I Esophageal Adenocarcinoma AJCC v8Phase 3NCT03801876
Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer
A Phase 3 study testing Biospecimen Collection, Capecitabine and Carboplatin in people with Clinical Stage I Esophageal Adenocarcinoma AJCC v8 and Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8, run by NRG Oncology at 96 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clinical Stage I Esophageal Adenocarcinoma AJCC v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8, Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8
- What is being tested?
- Biospecimen Collection, Capecitabine and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 96 sitesUnited States
- Study dates
- 26 Jun 2019to 7 Nov 2036
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
96 sites in 1 country.
96 sites in 1 country
United States96 sites
Mayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, 56007
Inova Alexandria Hospital
Alexandria, Virginia, 22304
Alton Memorial Hospital
Alton, Illinois, 62002
Emory Proton Therapy Center
Atlanta, Georgia, 30308
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011
Maryland Proton Treatment Center
Baltimore, Maryland, 21201
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Geauga Hospital
Chardon, Ohio, 44024
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Case Western Reserve University
Cleveland, Ohio, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Memorial Sloan Kettering Commack
Commack, New York, 11725
MD Anderson in The Woodlands
Conroe, Texas, 77384
Mercy Hospital
Coon Rapids, Minnesota, 55433
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, 54701
Mercy Cancer Center-Elyria
Elyria, Ohio, 44035
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
McLaren Cancer Institute-Flint
Flint, Michigan, 48532
Unity Hospital
Fridley, Minnesota, 55432
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
UT MD Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
Covenant Health Proton Center
Knoxville, Tennessee, 37909
Covenant Health Cancer Centers
Knoxville, Tennessee, 37916
Covenant Health Cancer Centers - West
Knoxville, Tennessee, 37932
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446
UT MD Anderson - League City
League City, Texas, 77573
Inova Loudoun Hospital
Leesburg, Virginia, 20176
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Mayo Clinic Health Systems-Mankato
Mankato, Minnesota, 56001
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Covenant Health Oncology Group - Maryville
Maryville, Tennessee, 37804
UH Seidman Cancer Center at Landerbrook Health Center
Mayfield Heights, Ohio, 44124
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Miami Cancer Institute
Miami, Florida, 33176
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights, Ohio, 44130
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
McLaren Cancer Institute-Central Michigan
Mount Pleasant, Michigan, 48858
New York Proton Center
New York, New York, 10035
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic Radiation Therapy-Northfield
Northfield, Minnesota, 55057
Covenant Health Oncology Group - Oak Ridge
Oak Ridge, Tennessee, 37830
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Orlando Health Cancer Institute
Orlando, Florida, 32806
McLaren Cancer Institute-Owosso
Owosso, Michigan, 48867
University Hospitals Parma Medical Center
Parma, Ohio, 44129
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
University Hospitals Portage Medical Center
Ravenna, Ohio, 44266
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
UH Seidman Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, 44870
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
University of Washington Medical Center - Montlake
Seattle, Washington, 98195
Memorial Hospital East
Shiloh, Illinois, 62269
Mercy Hospital Springfield
Springfield, Missouri, 65804
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital South
St Louis, Missouri, 63128
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
MD Anderson in Sugar Land
Sugar Land, Texas, 77478
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Ridgeview Medical Center
Waconia, Minnesota, 55387
University Hospitals Sharon Health Center
Wadsworth, Ohio, 44281
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, 44145
UHHS-Westlake Medical Center
Westlake, Ohio, 44145
About this study
Official title: Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- To compare the total toxicity burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.
EXPLORATORY OBJECTIVES:
- 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.
- 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
- Being tested
- Biospecimen Collection, Capecitabine, Carboplatin, Computed Tomography, Docetaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
CapecitabineDrug
Also called Ro 09-1978/000, Xeloda
Oral
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or PET/CT
DocetaxelDrug
Also called Docecad, RP 56976, RP-56976, RP56976
IV
EsophagectomyProcedure or surgery
Also called excision of the esophagus
Undergo esophagectomy
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
IV
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy
Undergo IMRT
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Oral
OxaliplatinDrug
Also called 1-OHP, Ai Heng, Aiheng, Dacotin
IV
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
Proton Beam Radiation TherapyRadiation
Also called External beam radiation therapy protons (procedure), External Beam Radiotherapy (protons), PBRT, Proton
Undergo PBT
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Group I (PBT, concurrent chemotherapy, esophagectomy) | Experimental | Patients undergo PBT 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 PBT. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study. Receives: Procedure: Biospecimen Collection; Drug: Capecitabine; Drug: Carboplatin; Procedure: Computed Tomography; Drug: Docetaxel; Procedure: Esophagectomy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Group II (IMRT, concurrent chemotherapy, esophagectomy) | Active comparator | 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. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study. Receives: 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; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test.
Measured: 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
Incidence of specific grade 3+ cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatment
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.
Measured: From baseline up to 8 years
Secondary outcomes (10)
Change in patient reported outcomes (PROs) of symptom and function
Will be assessed using the MD Anderson Symptom Inventory (MDASI) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue tools. The primary analysis cohorts for PRO endpoints will be intent-to-treat, with sensitivity analyses done limited to patients that started protocol treatment. General linear models with maximum likelihood estimation will be used to assess MDASI symptom severity and functioning trends across time as the primary PRO endpoints. Mean change (follow-up time point - baseline score) in fatigue will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead. Additionally, a general linear model with maximum likelihood estimation will be used to assess fatigue trends across time.
Measured: Baseline up to 12 months after end of chemoradiation
Pathologic response rate
A Chi-square test will be used to compare the pathologic response rates between the treatment arms.
Measured: At time of surgery
Length of hospitalization
Will be defined as number of days in the hospital post protocol-defined surgery. Mean hospitalization days will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
Measured: From baseline up to 8 years
Grade 4 lymphopenia during chemoradiation
Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients experiencing grade 4 lymphopenia during chemoradiation will be compared between treatment arms using a chi-squared test.
Measured: From baseline up to 8 years
Lymphocyte counts
Mean lymphocyte counts at first post chemoradiation follow-up will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
Measured: From baseline up to 8 years
Locoregional failure (LRF)
Will be defined as local/regional recurrence or progression. Will be estimated by the cumulative incidence method, with death as a competing risk. The distribution of LRF estimates between the two arms will be compared using Gray's test. The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LRF.
Measured: From the date of randomization to the date of first LRF or date of last follow-up for patients without an LRF event reported, assessed up to 8 years
Distant metastatic-free survival (DMFS)
Will be defined as appearance of distant metastasis or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with DMFS.
Measured: From the date of randomization to the date of first DMFS failure or last follow-up for patients without a reported DMFS event, assessed up to 8 years
Progression-free survival
Will be defined as appearance of local/regional/distant failure or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS.
Measured: From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 8 years
Quality-adjusted life years (QALY)
Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met.
Measured: Assessed up to 8 years
Cost-benefit economic analysis of treatment
Will be calculated by the visual analog scale (VAS) and index scores form the EQ-5D-5L only be done if primary endpoint is met. Will be compared between treatment arms using a t-test with a 2-sided significance level of 0.05. If there are significant differences, then a cost analysis will be conducted.
Measured: Assessed up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start26 Jun 2019
- Primary completion7 Nov 2031 (estimated)
- Study completion7 Nov 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clinical Stage I Esophageal Adenocarcinoma AJCC v8Studies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Steven H Lin, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801876
- Sponsor's protocol ID
- NRG-GI006
- Other IDs
- NCI-2018-03378, NRG-GI006, NRG-GI006, U10CA180822, U10CA180868
- Status last verified
- Aug 2026
- First submitted
- 3 Jan 2019
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Publications
Muijs CT, Klaver YLB, Nuyttens J, Lips IM, Muller K, Ebrahimi GM, Dankers FJWM, Verhoeven R, Schuit E, Berbee M. National indication protocol for proton radiotherapy in esophageal cancer patients in the Netherlands. Radiother Oncol. 2025 Dec;213:111164. doi: 10.1016/j.radonc.2025.111164. Epub 2025 Sep 24.
PubMed 41005671