Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer
Esophogeal Cancer
Unknown Primary
18 Years and older, Male and Female
NRG-GI006 (primary)
NRG-GI006
NCI-2018-03378
Summary
This trial studies how well proton beam radiation therapy compared with intensity modulated photo 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 photo radiotherapy will work better in treating patients with esophageal cancer.
Objectives
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.
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.
X. To compare the total toxicity burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.
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 chemotherapy consisting of carboplatin/paclitaxel, or fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX)/capecitabine-oxaliplatin (CAPOX), or docetaxel/fluorouracil (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 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 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.
Eligibility
- 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 > 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
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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