Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Trial
Official title:
Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
Verified date | February 2024 |
Source | NRG Oncology |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Recruiting |
Enrollment | 300 |
Est. completion date | December 21, 2031 |
Est. primary completion date | December 21, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 will be allowed as the induction chemotherapy regimen. - 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 |
Country | Name | City | State |
---|---|---|---|
United States | Mayo Clinic Health System in Albert Lea | Albert Lea | Minnesota |
United States | Inova Alexandria Hospital | Alexandria | Virginia |
United States | Alton Memorial Hospital | Alton | Illinois |
United States | Emory Proton Therapy Center | Atlanta | Georgia |
United States | Emory Saint Joseph's Hospital | Atlanta | Georgia |
United States | Emory University Hospital Midtown | Atlanta | Georgia |
United States | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia |
United States | UH Seidman Cancer Center at UH Avon Health Center | Avon | Ohio |
United States | Maryland Proton Treatment Center | Baltimore | Maryland |
United States | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland |
United States | Memorial Sloan Kettering Basking Ridge | Basking Ridge | New Jersey |
United States | McLaren Cancer Institute-Bay City | Bay City | Michigan |
United States | UHHS-Chagrin Highlands Medical Center | Beachwood | Ohio |
United States | UM Upper Chesapeake Medical Center | Bel Air | Maryland |
United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
United States | Geauga Hospital | Chardon | Ohio |
United States | University of Cincinnati Cancer Center-UC Medical Center | Cincinnati | Ohio |
United States | Case Western Reserve University | Cleveland | Ohio |
United States | Memorial Sloan Kettering Commack | Commack | New York |
United States | MD Anderson in The Woodlands | Conroe | Texas |
United States | Mercy Hospital | Coon Rapids | Minnesota |
United States | UM Sylvester Comprehensive Cancer Center at Coral Gables | Coral Gables | Florida |
United States | Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri |
United States | Beaumont Hospital - Dearborn | Dearborn | Michigan |
United States | UM Sylvester Comprehensive Cancer Center at Deerfield Beach | Deerfield Beach | Florida |
United States | Northwestern Medicine Cancer Center Kishwaukee | DeKalb | Illinois |
United States | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan |
United States | Mayo Clinic Health System-Eau Claire Clinic | Eau Claire | Wisconsin |
United States | Mercy Cancer Center-Elyria | Elyria | Ohio |
United States | Inova Fair Oaks Hospital | Fairfax | Virginia |
United States | Inova Schar Cancer Institute | Fairfax | Virginia |
United States | Weisberg Cancer Treatment Center | Farmington Hills | Michigan |
United States | McLaren Cancer Institute-Flint | Flint | Michigan |
United States | Unity Hospital | Fridley | Minnesota |
United States | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois |
United States | Memorial Sloan Kettering Westchester | Harrison | New York |
United States | M D Anderson Cancer Center | Houston | Texas |
United States | MD Anderson West Houston | Houston | Texas |
United States | Thompson Cancer Survival Center | Knoxville | Tennessee |
United States | Thompson Cancer Survival Center - West | Knoxville | Tennessee |
United States | Thompson Proton Center | Knoxville | Tennessee |
United States | Karmanos Cancer Institute at McLaren Greater Lansing | Lansing | Michigan |
United States | McLaren Cancer Institute-Lapeer Region | Lapeer | Michigan |
United States | MD Anderson League City | League City | Texas |
United States | Inova Loudoun Hospital | Leesburg | Virginia |
United States | Mayo Clinic Health Systems-Mankato | Mankato | Minnesota |
United States | Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota |
United States | Thompson Oncology Group-Maryville | Maryville | Tennessee |
United States | UH Seidman Cancer Center at Landerbrook Health Center | Mayfield Heights | Ohio |
United States | UH Seidman Cancer Center at Lake Health Mentor Campus | Mentor | Ohio |
United States | Miami Cancer Institute | Miami | Florida |
United States | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida |
United States | UH Seidman Cancer Center at Southwest General Hospital | Middleburg Heights | Ohio |
United States | Memorial Sloan Kettering Monmouth | Middletown | New Jersey |
United States | Hennepin County Medical Center | Minneapolis | Minnesota |
United States | Memorial Sloan Kettering Bergen | Montvale | New Jersey |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | New York Proton Center | New York | New York |
United States | Mayo Clinic Radiation Therapy-Northfield | Northfield | Minnesota |
United States | Thompson Oncology Group-Oak Ridge | Oak Ridge | Tennessee |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | Orlando Health Cancer Institute | Orlando | Florida |
United States | McLaren Cancer Institute-Owosso | Owosso | Michigan |
United States | University Hospitals Parma Medical Center | Parma | Ohio |
United States | University of Pennsylvania/Abramson Cancer Center | Philadelphia | Pennsylvania |
United States | Mayo Clinic Hospital in Arizona | Phoenix | Arizona |
United States | University Hospitals Portage Medical Center | Ravenna | Ohio |
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
United States | William Beaumont Hospital-Royal Oak | Royal Oak | Michigan |
United States | Siteman Cancer Center at Christian Hospital | Saint Louis | Missouri |
United States | Siteman Cancer Center-South County | Saint Louis | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Siteman Cancer Center at Saint Peters Hospital | Saint Peters | Missouri |
United States | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah |
United States | UH Seidman Cancer Center at Firelands Regional Medical Center | Sandusky | Ohio |
United States | Mayo Clinic in Arizona | Scottsdale | Arizona |
United States | University of Washington Medical Center - Montlake | Seattle | Washington |
United States | Memorial Hospital East | Shiloh | Illinois |
United States | MD Anderson in Sugar Land | Sugar Land | Texas |
United States | William Beaumont Hospital - Troy | Troy | Michigan |
United States | Memorial Sloan Kettering Nassau | Uniondale | New York |
United States | University Hospitals Sharon Health Center | Wadsworth | Ohio |
United States | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois |
United States | University of Cincinnati Cancer Center-West Chester | West Chester | Ohio |
United States | UH Seidman Cancer Center at Saint John Medical Center | Westlake | Ohio |
United States | UHHS-Westlake Medical Center | Westlake | Ohio |
Lead Sponsor | Collaborator |
---|---|
NRG Oncology | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | 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 | |
Primary | 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. | From baseline up to 8 years | |
Secondary | Pathologic response rate | A Chi-square test will be used to compare the pathologic response rates between the treatment arms. | At time of surgery | |
Secondary | 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. | From the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days | |
Secondary | 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. | From the last date of chemoradiation up to 8 weeks post chemoradiation | |
Secondary | 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. | 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 | |
Secondary | 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. | 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 | |
Secondary | 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. | 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 | |
Secondary | Quality-adjusted life years (QALY) | Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met. | Assessed up to 8 years | |
Secondary | 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. | Assessed up to 8 years |
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