Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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
  • 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)
  • Creatinine clearance > 50 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
  • Symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia not controlled by pacer device 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group I (PBT, paclitaxel, carboplatin, esophagectomy)
Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive paclitaxel (50 mg/m^2) IV and carboplatin (AUC=2 [maximum 300 mg]) IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Procedure: Esophagectomy
    Undergo esophagectomy
    Other names:
    • excision of the esophagus
  • Drug: Paclitaxel
    Given IV
    Other names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Radiation: Proton Beam Radiation Therapy
    Undergo PBT
    Other names:
    • PBRT
    • Proton Radiation Therapy
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other names:
    • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Active Comparator
Group II (IMRT, paclitaxel, carboplatin, esophagectomy)
Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive paclitaxel (50 mg/m^2) IV and carboplatin (AUC=2 [maximum 300 mg]) IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
  • Drug: Carboplatin
    Given IV
    Other names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Procedure: Esophagectomy
    Undergo esophagectomy
    Other names:
    • excision of the esophagus
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
  • Drug: Paclitaxel
    Given IV
    Other names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other names:
    • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

Recruiting Locations

Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
Contact:
Site Public Contact
877-726-5130

More Details

Status
Recruiting
Sponsor
NRG Oncology

Study Contact

Detailed Description

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.

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.

V. 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.

EXPLORATORY OBJECTIVES:

I. 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 paclitaxel intravenously (IV) and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT.

GROUP II: Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT.

In both groups, within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.

After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually thereafter.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.