Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- NRG Oncology
- 入组人数
- 300
- 试验地点
- 250
- 主要终点
- Overall survival (OS)
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
I. 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:
I. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Esophagectomy (Procedure)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Positron Emission Tomography (Procedure)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Proton Beam Radiation Therapy (Radiation)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Quality-of-Life Assessment (Other)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Questionnaire Administration (Other)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Computed Tomography (Procedure)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Esophagectomy (Procedure)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Positron Emission Tomography (Procedure)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Capecitabine (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Carboplatin (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Docetaxel (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Fluorouracil (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Leucovorin Calcium (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Oxaliplatin (Drug)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Paclitaxel (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Capecitabine (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Carboplatin (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Fluorouracil (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Paclitaxel (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Oxaliplatin (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Biospecimen Collection (Procedure)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Quality-of-Life Assessment (Other)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Biospecimen Collection (Procedure)
Group I (PBT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Computed Tomography (Procedure)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Docetaxel (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Leucovorin Calcium (Drug)
Group II (IMRT, concurrent chemotherapy, esophagectomy)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Overall survival (OS)
时间窗: 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 treatment
时间窗: From 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.
次要结局
- Pathologic response rate(At time of surgery)
- Locoregional failure (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)
- Distant metastatic-free survival (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)
- Progression-free survival(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)(Assessed up to 8 years)
- Cost-benefit economic analysis of treatment(Assessed up to 8 years)
- Change in patient reported outcomes (PROs) of symptom and function(Baseline up to 12 months after end of chemoradiation)
- Pathologic response rate(At time of surgery)
- Length of hospitalization(From baseline up to 8 years)
- Grade 4 lymphopenia during chemoradiation(From baseline up to 8 years)
- Lymphocyte counts(From baseline up to 8 years)
- Locoregional failure (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)
- Distant metastatic-free survival (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)
- Progression-free survival(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)(Assessed up to 8 years)
- Cost-benefit economic analysis of treatment(Assessed up to 8 years)