Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

Sponsor

NRG Oncology (Other)

Overall Status

Recruiting

CT.gov ID

NCT03801876

Collaborator

National Cancer Institute (NCI) (NIH)

300

Enrollment

Locations

Arms

154.6

Anticipated Duration (Months)

4.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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 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.

Condition or Disease	Intervention/Treatment	Phase
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 Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8 Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage III Esophageal Adenocarcinoma AJCC v8 Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8 Clinical Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage I Esophageal Adenocarcinoma AJCC v8 Pathologic Stage I Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IC Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage II Esophageal Adenocarcinoma AJCC v8 Pathologic Stage II Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage III Esophageal Adenocarcinoma AJCC v8 Pathologic Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage I Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage I Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage II Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage II Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage III Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage III Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Thoracic Esophagus Squamous Cell Carcinoma	Drug: Carboplatin Procedure: Esophagectomy Radiation: Intensity-Modulated Radiation Therapy Drug: Paclitaxel Radiation: Proton Beam Radiation Therapy Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: FOLFOX regimen Drug: CAPOX regimen Drug: Docetaxel Drug: 5FU	Phase 3

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.
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.
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.
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.
To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT.
To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT & IMRT.
To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT.
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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer

Actual Study Start Date :

Mar 15, 2019

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Feb 1, 2032

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I (PBT, Chemotherapy, 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 chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards 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 Drug: FOLFOX regimen Folinic acid, flurouracil and oxaliplatin Other Names: FOLFOX Drug: CAPOX regimen Capecitabine combined with oxaliplatin Other Names: CAPE-OX OxCap Drug: Docetaxel Chemotherapy Other Names: Taxotere Drug: 5FU Chemotherapy Other Names: 5-FU flurouracil Tolak Fluoroplex Efudex Carac Adrucil
Active Comparator: Group II (IMRT, Chemotherapy, 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 chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards 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 Drug: FOLFOX regimen Folinic acid, flurouracil and oxaliplatin Other Names: FOLFOX Drug: CAPOX regimen Capecitabine combined with oxaliplatin Other Names: CAPE-OX OxCap Drug: Docetaxel Chemotherapy Other Names: Taxotere Drug: 5FU Chemotherapy Other Names: 5-FU flurouracil Tolak Fluoroplex Efudex Carac Adrucil

Arm

Intervention/Treatment

Experimental: Group I (PBT, Chemotherapy, 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 chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards 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

Drug: FOLFOX regimen

Folinic acid, flurouracil and oxaliplatin

Other Names:

FOLFOX

Drug: CAPOX regimen

Capecitabine combined with oxaliplatin

Other Names:

CAPE-OX

OxCap

Drug: Docetaxel

Chemotherapy

Other Names:

Taxotere

Drug: 5FU

Chemotherapy

Other Names:

5-FU

flurouracil

Tolak

Fluoroplex

Efudex

Carac

Adrucil

Active Comparator: Group II (IMRT, Chemotherapy, 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 chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU [with capecitabine as an acceptable substitute for 5-FU]) per institutional standards 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

Drug: FOLFOX regimen

Folinic acid, flurouracil and oxaliplatin

Other Names:

FOLFOX

Drug: CAPOX regimen

Capecitabine combined with oxaliplatin

Other Names:

CAPE-OX

OxCap

Drug: Docetaxel

Chemotherapy

Other Names:

Taxotere

Drug: 5FU

Chemotherapy

Other Names:

5-FU

flurouracil

Tolak

Fluoroplex

Efudex

Carac

Adrucil

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [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 [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.

Secondary Outcome Measures

Pathologic response rate [At time of surgery]
A Chi-square test will be used to compare the pathologic response rates between the treatment arms.
Grade 4 lymphopenia during chemoradiation [From the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days]
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.
Lymphocyte counts [From the last date of chemoradiation up to 8 weeks post chemoradiation]
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.
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]
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.
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]
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.
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]
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.
Quality-adjusted life years (QALY) [Assessed up to 8 years]
Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met.
Cost-benefit economic analysis of treatment [Assessed up to 8 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital in Arizona	Phoenix	Arizona	United States	85054
2	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
3	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida	United States	33146
4	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
5	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
6	Miami Cancer Institute	Miami	Florida	United States	33176
7	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
8	Emory Proton Therapy Center	Atlanta	Georgia	United States	30308
9	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
10	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
11	Emory Saint Joseph's Hospital	Atlanta	Georgia	United States	30342
12	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois	United States	60115
13	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
14	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
15	Maryland Proton Treatment Center	Baltimore	Maryland	United States	21201
16	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
17	UM Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
18	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
19	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
20	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
21	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
22	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota	United States	56007
23	Unity Hospital	Fridley	Minnesota	United States	55432
24	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota	United States	56001
25	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
26	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
27	Mayo Clinic Radiation Therapy-Northfield	Northfield	Minnesota	United States	55057
28	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
29	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
30	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
31	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
32	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri	United States	63136
33	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
34	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
35	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
36	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
37	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
38	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
39	New York Proton Center	New York	New York	United States	10035
40	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
41	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
42	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	United States	44122
43	Geauga Hospital	Chardon	Ohio	United States	44024
44	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
45	Case Western Reserve University	Cleveland	Ohio	United States	44106
46	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
47	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio	United States	44124
48	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
49	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio	United States	44130
50	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
51	University Hospitals Portage Medical Center	Ravenna	Ohio	United States	44266
52	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
53	University Hospitals Sharon Health Center	Wadsworth	Ohio	United States	44281
54	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio	United States	45069
55	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio	United States	44145
56	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
57	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
58	MD Anderson in The Woodlands	Conroe	Texas	United States	77384
59	M D Anderson Cancer Center	Houston	Texas	United States	77030
60	MD Anderson West Houston	Houston	Texas	United States	77079
61	MD Anderson League City	League City	Texas	United States	77573
62	MD Anderson in Sugar Land	Sugar Land	Texas	United States	77478
63	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
64	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
65	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin	United States	54701