Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01196390
• Collaborator: NRG Oncology (Other)
• Enrollment: 203
• Locations: 634
• Arms: 2
• Patients Per Site: 0.3

Study Details

Study Description

Brief Summary

This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Stage IB Esophageal Cancer AJCC v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7	Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Biological: Trastuzumab	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma.

SECONDARY OBJECTIVES:

1. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma.

2. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma.

3. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab.

4. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation.

5. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma.

PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES:

1. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score.

2. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response.

3. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation.

4. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E.

5. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36.

Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.

After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 203 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma
• Actual Study Start Date: Dec 30, 2010
• Actual Primary Completion Date: Dec 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (radiotherapy, chemotherapy, trastuzumab) Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel intravenously IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; 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 ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Biological: Trastuzumab; Given IV; Other Names: ABP 980 ALT02 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 Herzuma Kanjinti MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 Ogivri Ontruzant PF-05280014 rhuMAb HER2 RO0452317 SB3 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar ALT02 trastuzumab biosimilar EG12014 Trastuzumab Biosimilar HLX02 Trastuzumab Biosimilar PF-05280014 Trastuzumab Biosimilar SB3 Trastuzumab Biosimilar SIBP-01 Trastuzumab-anns Trastuzumab-dkst Trastuzumab-dttb Trastuzumab-pkrb Trastuzumab-qyyp Trazimera
Experimental: Arm II (radiotherapy and chemotherapy) Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; 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 ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Disease-free Survival (DFS) [From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.]

   A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.

Secondary Outcome Measures

1. Percentage of Participants With Pathologic Complete Response at Surgery [At the time of surgery, 5-8 weeks after completion of radiation therapy.]

   Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.

2. Overall Survival [From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.]

   Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.

3. Frequency of Highest Grade Adverse Event Per Participant [From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.]

   Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.

4. Health-related Quality of Life (QOL) [Baseline, 6 weeks after end of radiation, 1 and 2 years from treatment start]

   Measured by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E). The FACT-E measures multidimensional quality of life in patients with esophagus cancer. Possible scores range from 0 to 68, with higher scores indicating a better outcome.

5. Quality-adjusted Survival [From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.]

6. Molecular Correlates of Efficacy [From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.]

7. Number of Participants With Any Cardiac Adverse Events Regardless of Attribution [From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.]

   Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm

• Endoscopy with biopsy

• PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION

• Intent to submit tissue for central HER2 testing

• Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up:

• Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing)

• Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =< 2 cm

• Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula

• Zubrod performance status 0-2

• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

• Platelets >= 100,000 cells/mm^3

• Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)

• Creatinine =< 2 times upper limit of normal

• Bilirubin =< 1.5 times upper limit of normal

• Aspartate aminotransferase (AST) =< 3.0 times upper limit of normal

• For women of childbearing potential, a negative serum or urine pregnancy test

• Patients must sign a study-specific informed consent prior to study entry

• CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY)

• HER2 expressing adenocarcinoma of the esophagus centrally

• Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration

• Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration

• Consultation with a medical oncologist within 56 days prior to step 2 registration

• Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up:

• History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration

• Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration)

• Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan

• Electrocardiogram (EKG) within 56 days prior to step 2 registration

• Serum creatinine =< 2 x the upper limit or normal within 14 days prior to step 2 registration

• Zubrod performance status 0-2 within 14 days prior to step 2 registration

• For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration

• Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration

• Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab

Exclusion Criteria:

• Patients with cervical esophageal carcinoma

• Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)

• Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable

• Prior radiation therapy for esophageal cancer or prior chest radiotherapy

• Prior anthracycline or taxane

• Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi

• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)

• Medical contraindications to esophagectomy

• Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor [EGFR]) pathway

• Prior therapy with trastuzumab

• Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody

• Previous history of congestive heart failure

• Severe, active comorbidity, defined as follows:

• Unstable angina in the last 6 months

• Transmural myocardial infarction within the last 6 months

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients

• Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	The Kirklin Clinic at Acton Road	Birmingham	Alabama	United States	35243
3	Providence Hospital	Mobile	Alabama	United States	36608
4	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	Mayo Clinic Hospital in Arizona	Phoenix	Arizona	United States	85054
10	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
11	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
12	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
13	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
14	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
15	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
16	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
17	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
18	Mercy San Juan Medical Center	Carmichael	California	United States	95608
19	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
20	Enloe Medical Center	Chico	California	United States	95926
21	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
22	Epic Care-Dublin	Dublin	California	United States	94568
23	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
24	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
25	Kaiser Permanente-Fremont	Fremont	California	United States	94538
26	Fresno Cancer Center	Fresno	California	United States	93720
27	Kaiser Permanente-Fresno	Fresno	California	United States	93720
28	Marin General Hospital	Greenbrae	California	United States	94904
29	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
30	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
31	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
32	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
33	Memorial Medical Center	Modesto	California	United States	95355
34	Kaiser Permanente-Modesto	Modesto	California	United States	95356
35	El Camino Hospital	Mountain View	California	United States	94040
36	Sutter Cancer Research Consortium	Novato	California	United States	94945
37	Highland General Hospital	Oakland	California	United States	94602
38	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
39	Bay Area Tumor Institute	Oakland	California	United States	94609
40	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
41	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
42	Kaiser Permanente-Oakland	Oakland	California	United States	94611
43	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
44	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
45	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
46	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
47	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
48	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
49	Kaiser Permanente-Richmond	Richmond	California	United States	94801
50	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
51	Kaiser Permanente-Roseville	Roseville	California	United States	95661
52	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
53	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
54	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
55	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
56	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
57	South Sacramento Cancer Center	Sacramento	California	United States	95823
58	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
59	Saint Helena Hospital	Saint Helena	California	United States	94574
60	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
61	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
62	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
63	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
64	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
65	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
66	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
67	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
68	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
69	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
70	Kaiser Permanente-Stockton	Stockton	California	United States	95210
71	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
72	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
73	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
74	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
75	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
76	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
77	The Medical Center of Aurora	Aurora	Colorado	United States	80012
78	Boulder Community Hospital	Boulder	Colorado	United States	80301
79	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
80	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
81	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
82	Porter Adventist Hospital	Denver	Colorado	United States	80210
83	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
84	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
85	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
86	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
87	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
88	Rose Medical Center	Denver	Colorado	United States	80220
89	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
90	Mercy Medical Center	Durango	Colorado	United States	81301
91	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
92	Swedish Medical Center	Englewood	Colorado	United States	80113
93	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
94	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
95	North Colorado Medical Center	Greeley	Colorado	United States	80631
96	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
97	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
98	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
99	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
100	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
101	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
102	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
103	Longmont United Hospital	Longmont	Colorado	United States	80501
104	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
105	McKee Medical Center	Loveland	Colorado	United States	80539
106	Parker Adventist Hospital	Parker	Colorado	United States	80138
107	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
108	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
109	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
110	North Suburban Medical Center	Thornton	Colorado	United States	80229
111	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
112	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
113	Hartford Hospital	Hartford	Connecticut	United States	06102
114	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
115	Midstate Medical Center	Meriden	Connecticut	United States	06451
116	Middlesex Hospital	Middletown	Connecticut	United States	06457
117	Yale University	New Haven	Connecticut	United States	06520
118	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
119	William Backus Hospital	Norwich	Connecticut	United States	06360
120	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
121	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
122	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
123	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
124	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
125	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
126	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
127	AdventHealth Altamonte	Altamonte Springs	Florida	United States	32701
128	AdventHealth Kissimmee	Kissimmee	Florida	United States	34744
129	Miami Cancer Institute	Miami	Florida	United States	33176
130	AdventHealth Orlando	Orlando	Florida	United States	32803
131	AdventHealth East Orlando	Orlando	Florida	United States	32822
132	Robert and Carol Weissman Cancer Center at Martin Health	Stuart	Florida	United States	34994
133	AdventHealth Winter Park	Winter Park	Florida	United States	32792
134	Grady Health System	Atlanta	Georgia	United States	30303
135	Piedmont Hospital	Atlanta	Georgia	United States	30309
136	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
137	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
138	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia	United States	30501
139	Medical Center of Central Georgia	Macon	Georgia	United States	31201
140	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
141	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
142	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
143	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
144	Saint Joseph Regional Medical Center	Lewiston	Idaho	United States	83501
145	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
146	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
147	Mac Neal Hospital	Berwyn	Illinois	United States	60402
148	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
149	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
150	Northwestern University	Chicago	Illinois	United States	60611
151	University of Illinois	Chicago	Illinois	United States	60612
152	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
153	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
154	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
155	Crossroads Cancer Center	Effingham	Illinois	United States	62401
156	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
157	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
158	Loyola University Medical Center	Maywood	Illinois	United States	60153
159	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
160	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
161	Spector, David MD (UIA Investigator)	Moline	Illinois	United States	61265
162	Trinity Medical Center	Moline	Illinois	United States	61265
163	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
164	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
165	West Suburban Medical Center	River Forest	Illinois	United States	60305
166	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
167	Memorial Medical Center	Springfield	Illinois	United States	62781
168	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
169	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
170	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
171	Elkhart General Hospital	Elkhart	Indiana	United States	46515
172	Radiation Oncology Associates PC	Fort Wayne	Indiana	United States	46804
173	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
174	Franciscan Health Indianapolis	Indianapolis	Indiana	United States	46237
175	Community Howard Regional Health	Kokomo	Indiana	United States	46904
176	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
177	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
178	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
179	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
180	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
181	Reid Health	Richmond	Indiana	United States	47374
182	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
183	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
184	South Bend Clinic	South Bend	Indiana	United States	46617
185	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
186	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
187	Mary Greeley Medical Center	Ames	Iowa	United States	50010
188	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
189	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
190	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
191	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
192	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
193	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
194	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
195	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
196	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
197	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
198	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
199	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
200	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
201	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
202	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
203	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
204	University of Kansas Cancer Center-West	Kansas City	Kansas	United States	66112
205	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
206	Menorah Medical Center	Overland Park	Kansas	United States	66209
207	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
208	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
209	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
210	Salina Regional Health Center	Salina	Kansas	United States	67401
211	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
212	Baptist Health Lexington	Lexington	Kentucky	United States	40503
213	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
214	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
215	Central Maine Medical Center	Lewiston	Maine	United States	04240
216	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
217	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
218	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
219	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
220	UM Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
221	TidalHealth Peninsula Regional	Salisbury	Maryland	United States	21801
222	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
223	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
224	Boston Medical Center	Boston	Massachusetts	United States	02118
225	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
226	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
227	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts	United States	01757
228	Berkshire Medical Center - Cancer Center	Pittsfield	Massachusetts	United States	01201
229	Dana-Farber/Brigham and Women's Cancer Center at South Shore	South Weymouth	Massachusetts	United States	02190
230	D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01107
231	Baystate Medical Center	Springfield	Massachusetts	United States	01199
232	Bixby Medical Center	Adrian	Michigan	United States	49221
233	Hickman Cancer Center	Adrian	Michigan	United States	49221
234	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
235	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
236	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
237	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan	United States	48183
238	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
239	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
240	Henry Ford Hospital	Detroit	Michigan	United States	48202
241	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
242	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
243	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
244	Hurley Medical Center	Flint	Michigan	United States	48503
245	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
246	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
247	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
248	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
249	Sparrow Hospital	Lansing	Michigan	United States	48912
250	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
251	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
252	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
253	Lakeland Hospital Niles	Niles	Michigan	United States	49120
254	Ascension Providence Hospitals - Novi	Novi	Michigan	United States	48374
255	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
256	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
257	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
258	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
259	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
260	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
261	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
262	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
263	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
264	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
265	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
266	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
267	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
268	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
269	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
270	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
271	Unity Hospital	Fridley	Minnesota	United States	55432
272	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
273	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
274	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
275	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
276	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
277	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
278	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
279	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
280	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
281	Regions Hospital	Saint Paul	Minnesota	United States	55101
282	United Hospital	Saint Paul	Minnesota	United States	55102
283	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
284	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
285	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
286	Singing River Hospital	Pascagoula	Mississippi	United States	39581
287	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
288	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
289	Cox Cancer Center Branson	Branson	Missouri	United States	65616
290	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
291	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
292	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
293	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
294	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
295	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
296	Freeman Health System	Joplin	Missouri	United States	64804
297	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
298	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
299	North Kansas City Hospital	Kansas City	Missouri	United States	64116
300	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
301	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
302	Research Medical Center	Kansas City	Missouri	United States	64132
303	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
304	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri	United States	64064
305	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
306	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
307	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
308	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
309	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
310	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
311	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
312	Mercy Hospital South	Saint Louis	Missouri	United States	63128
313	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
314	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
315	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
316	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
317	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
318	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
319	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
320	CoxHealth South Hospital	Springfield	Missouri	United States	65807
321	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
322	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
323	Billings Clinic Cancer Center	Billings	Montana	United States	59101
324	Saint Vincent Healthcare	Billings	Montana	United States	59101
325	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
326	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
327	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
328	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
329	Saint Peter's Community Hospital	Helena	Montana	United States	59601
330	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
331	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
332	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
333	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
334	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
335	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
336	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
337	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
338	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
339	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
340	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
341	GenesisCare USA - Henderson	Henderson	Nevada	United States	89074
342	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
343	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
344	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
345	GenesisCare USA - Las Vegas	Las Vegas	Nevada	United States	89109
346	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
347	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
348	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
349	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
350	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
351	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
352	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada	United States	89128
353	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
354	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
355	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
356	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
357	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
358	GenesisCare USA - Fort Apache	Las Vegas	Nevada	United States	89148
359	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
360	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
361	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
362	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
363	Renown Regional Medical Center	Reno	Nevada	United States	89502
364	Concord Hospital	Concord	New Hampshire	United States	03301
365	Wentworth-Douglass Hospital	Dover	New Hampshire	United States	03820
366	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
367	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
368	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
369	Morristown Medical Center	Morristown	New Jersey	United States	07960
370	Virtua Memorial	Mount Holly	New Jersey	United States	08060
371	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07101
372	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
373	Capital Health Medical Center-Hopewell	Pennington	New Jersey	United States	08534
374	Sparta Cancer Treatment Center	Sparta	New Jersey	United States	07871
375	Overlook Hospital	Summit	New Jersey	United States	07902
376	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
377	Virtua Voorhees	Voorhees	New Jersey	United States	08043
378	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
379	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
380	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
381	Sands Cancer Center	Canandaigua	New York	United States	14424
382	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
383	Glens Falls Hospital	Glens Falls	New York	United States	12801
384	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
385	Mount Sinai Union Square	New York	New York	United States	10003
386	Mount Sinai West	New York	New York	United States	10019
387	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
388	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
389	Wilmot Cancer Institute Radiation Oncology at Greece	Rochester	New York	United States	14606
390	Highland Hospital	Rochester	New York	United States	14620
391	University of Rochester	Rochester	New York	United States	14642
392	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York	United States	10591
393	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
394	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
395	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
396	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina	United States	28210
397	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina	United States	28025
398	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
399	Matthews Radiation Oncology Center	Matthews	North Carolina	United States	28105
400	Atrium Health Union/LCI-Union	Monroe	North Carolina	United States	28112
401	UNC Rex Cancer Center	Raleigh	North Carolina	United States	27607
402	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
403	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
404	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
405	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
406	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
407	Summa Health System - Barberton Campus	Barberton	Ohio	United States	44203
408	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	United States	44122
409	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
410	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
411	Geauga Hospital	Chardon	Ohio	United States	44024
412	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
413	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
414	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
415	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
416	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio	United States	45230
417	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
418	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
419	Case Western Reserve University	Cleveland	Ohio	United States	44106
420	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
421	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
422	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
423	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
424	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
425	Grant Medical Center	Columbus	Ohio	United States	43215
426	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
427	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
428	Doctors Hospital	Columbus	Ohio	United States	43228
429	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
430	Miami Valley Hospital	Dayton	Ohio	United States	45409
431	Miami Valley Hospital North	Dayton	Ohio	United States	45415
432	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
433	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
434	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
435	Grady Memorial Hospital	Delaware	Ohio	United States	43015
436	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
437	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
438	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
439	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
440	Wayne Hospital	Greenville	Ohio	United States	45331
441	Kettering Medical Center	Kettering	Ohio	United States	45429
442	Fairfield Medical Center	Lancaster	Ohio	United States	43130
443	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
444	Lima Memorial Hospital	Lima	Ohio	United States	45804
445	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
446	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
447	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
448	Summa Health Medina Medical Center	Medina	Ohio	United States	44256
449	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
450	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio	United States	44130
451	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
452	Licking Memorial Hospital	Newark	Ohio	United States	43055
453	Newark Radiation Oncology	Newark	Ohio	United States	43055
454	Saint Charles Hospital	Oregon	Ohio	United States	43616
455	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
456	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
457	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
458	University Hospitals Portage Medical Center	Ravenna	Ohio	United States	44266
459	UH Seidman Cancer Center at Salem Regional Medical Center	Salem	Ohio	United States	44460
460	North Coast Cancer Care	Sandusky	Ohio	United States	44870
461	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
462	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
463	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
464	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
465	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
466	University of Toledo	Toledo	Ohio	United States	43614
467	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
468	Mercy Health - Saint Anne Hospital	Toledo	Ohio	United States	43623
469	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
470	Upper Valley Medical Center	Troy	Ohio	United States	45373
471	Fulton County Health Center	Wauseon	Ohio	United States	43567
472	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio	United States	45069
473	Saint Ann's Hospital	Westerville	Ohio	United States	43081
474	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
475	Cancer Treatment Center	Wooster	Ohio	United States	44691
476	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
477	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
478	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
479	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
480	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
481	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
482	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
483	Providence Portland Medical Center	Portland	Oregon	United States	97213
484	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
485	Salem Hospital	Salem	Oregon	United States	97301
486	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania	United States	15009
487	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
488	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
489	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
490	Northeast Radiation Oncology Center	Dunmore	Pennsylvania	United States	18512
491	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
492	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania	United States	15901
493	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
494	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania	United States	15108
495	Allegheny Valley Hospital	Natrona Heights	Pennsylvania	United States	15065
496	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania	United States	15065
497	UPMC Jameson	New Castle	Pennsylvania	United States	16105
498	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
499	American College of Radiology Imaging Network	Philadelphia	Pennsylvania	United States	19103
500	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
501	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
502	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania	United States	19114
503	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
504	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
505	UPMC-Saint Margaret	Pittsburgh	Pennsylvania	United States	15215
506	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
507	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania	United States	15236
508	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania	United States	15237
509	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania	United States	15243
510	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
511	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania	United States	15401
512	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania	United States	15301
513	Reading Hospital	West Reading	Pennsylvania	United States	19611
514	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania	United States	15090
515	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
516	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
517	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
518	Rhode Island Hospital	Providence	Rhode Island	United States	02903
519	Radiation Oncology Associates Incorporated	Providence	Rhode Island	United States	02904
520	Miriam Hospital	Providence	Rhode Island	United States	02906
521	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
522	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
523	Medical University of South Carolina	Charleston	South Carolina	United States	29425
524	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
525	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
526	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
527	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
528	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
529	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
530	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
531	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina	United States	29730
532	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
533	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
534	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee	United States	37660
535	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
536	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
537	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
538	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
539	Houston Methodist Hospital	Houston	Texas	United States	77030
540	UTMB Cancer Center at Victory Lakes	League City	Texas	United States	77573
541	Covenant Medical Center-Lakeside	Lubbock	Texas	United States	79410
542	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah	United States	84003
543	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
544	Logan Regional Hospital	Logan	Utah	United States	84321
545	Intermountain Medical Center	Murray	Utah	United States	84107
546	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
547	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
548	Saint George Regional Medical Center	Saint George	Utah	United States	84770
549	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
550	LDS Hospital	Salt Lake City	Utah	United States	84143
551	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont	United States	05819
552	Danville Regional Medical Center	Danville	Virginia	United States	24541
553	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
554	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
555	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
556	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
557	Overlake Medical Center	Bellevue	Washington	United States	98004
558	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
559	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
560	Harrison Medical Center	Bremerton	Washington	United States	98310
561	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
562	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
563	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
564	Saint Francis Hospital	Federal Way	Washington	United States	98003
565	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
566	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
567	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
568	Saint Clare Hospital	Lakewood	Washington	United States	98499
569	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
570	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
571	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
572	Capital Medical Center	Olympia	Washington	United States	98507
573	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
574	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
575	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
576	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
577	Kaiser Permanente Washington	Seattle	Washington	United States	98112
578	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
579	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
580	Olympic Medical Cancer Care Center	Sequim	Washington	United States	98384
581	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
582	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
583	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
584	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
585	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
586	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
587	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
588	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
589	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
590	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
591	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
592	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
593	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
594	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
595	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
596	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
597	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
598	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
599	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
600	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
601	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
602	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
603	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
604	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
605	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
606	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
607	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
608	Marshfield Medical Center	Marshfield	Wisconsin	United States	54449
609	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
610	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
611	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
612	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
613	Zablocki Veterans Administration Medical Center	Milwaukee	Wisconsin	United States	53295
614	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
615	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
616	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
617	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
618	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
619	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
620	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
621	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
622	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
623	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
624	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
625	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
626	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
627	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
628	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
629	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
630	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin	United States	53095
631	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
632	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
633	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
634	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Howard P Safran, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 15, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01196390
• Other Study ID Numbers: NCI-2011-02601; NCI-2011-02601; CDR0000683717; RTOG-1010; RTOG-1010; RTOG-1010; U10CA180830; U10CA180868; U10CA021661
• First Posted: Sep 8, 2010
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Paclitaxel; Carboplatin; Trastuzumab; Albumin-Bound Paclitaxel; Trastuzumab biosimilar HLX02; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	After registration, sites were required to submit participant tumor tissue for central human epidermal growth factor receptor 2 (HER2) testing. Only HER2-positive participants continued to randomization. In total, 571 participants were registered and 203 were randomized.

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Period Title: Overall Study
STARTED	102	101
Eligible	98	96
Eligible and Started Study Treatment	95	96
Eligible and Had Surgery	82	78
COMPLETED	98	96
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation	Total
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery	Total of all reporting groups
Overall Participants	98	96	194
Age, Customized (Count of Participants)
≤ 39 years	0 0%	5 5.2%	5 2.6%
40-49 years	6 6.1%	7 7.3%	13 6.7%
50-59 years	30 30.6%	21 21.9%	51 26.3%
60-69 years	40 40.8%	31 32.3%	71 36.6%
70-79 years	20 20.4%	29 30.2%	49 25.3%
≥ 80 years	2 2%	3 3.1%	5 2.6%
Sex: Female, Male (Count of Participants)
Female	13 13.3%	17 17.7%	30 15.5%
Male	85 86.7%	79 82.3%	164 84.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1%	5 5.2%	6 3.1%
Not Hispanic or Latino	96 98%	89 92.7%	185 95.4%
Unknown or Not Reported	1 1%	2 2.1%	3 1.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 2.1%	2 1%
Asian	3 3.1%	0 0%	3 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1%	0 0%	1 0.5%
White	94 95.9%	92 95.8%	186 95.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 2.1%	2 1%
Zubrod Performance Status (Count of Participants)
0	62 63.3%	62 64.6%	124 63.9%
1	34 34.7%	31 32.3%	65 33.5%
2	2 2%	3 3.1%	5 2.6%
T stage, clinical (Count of Participants)
T1	1 1%	4 4.2%	5 2.6%
T2	18 18.4%	17 17.7%	35 18%
T3	79 80.6%	75 78.1%	154 79.4%
N stage, clinical (Count of Participants)
N0	27 27.6%	29 30.2%	56 28.9%
N1	55 56.1%	48 50%	103 53.1%
N2	16 16.3%	19 19.8%	35 18%
Presence of Adenopathy (Count of Participants)
No	38 38.8%	38 39.6%	76 39.2%
Yes adenopathy, but celiac absent	48 49%	48 50%	96 49.5%
Yes adenopathy and celiac present ≤ 2 cm	12 12.2%	10 10.4%	22 11.3%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS)
Description	A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported.
Time Frame	From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.

Outcome Measure Data

Analysis Population Description

Eligible randomized participants

Arm/Group Title	Chemoradiation and Trastuzumab (Arm 1)	Chemoradiation (Arm 2)
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	98	96
Median (95% Confidence Interval) [months]	19.6	14.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation and Trastuzumab (Arm 1), Chemoradiation (Arm 2)
	Comments	Assuming a median DFS time of 15 months (Arm 2), hypothesized increase in DFS corresponding to median DFS time of 25 months (Arm 1). Assuming an exponential distribution and constant hazards, 183 HER2-positive participants accrued over 5 years and followed for 3 years would result in 162 disease-free survival events and provide 90% statistical power to detect this difference with a 2-sided α of 0.05 and 2 interim analyses. See Limitations and Caveats section.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	Log Rank
	Comments	Two-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Chemoradiation arm

2. Secondary Outcome

Title	Percentage of Participants With Pathologic Complete Response at Surgery
Description	Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor.
Time Frame	At the time of surgery, 5-8 weeks after completion of radiation therapy.

Outcome Measure Data

Analysis Population Description

Eligible participants who had surgery

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	82	78
Number (95% Confidence Interval) [percentage of participants]	27 27.6%	29 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation and Trastuzumab (Arm 1), Chemoradiation (Arm 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Chi-squared
	Comments	Two-sided significance level = 0.05

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported.
Time Frame	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

Outcome Measure Data

Analysis Population Description

Eligible randomized participants

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	98	96
Median (95% Confidence Interval) [months]	38.5	38.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation and Trastuzumab (Arm 1), Chemoradiation (Arm 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Log Rank
	Comments	Two-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Chemoradiation arm

4. Secondary Outcome

Title	Frequency of Highest Grade Adverse Event Per Participant
Description	Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data.
Time Frame	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	95	96
Grade 1	0 0%	0 0%
Grade 2	14 14.3%	12 12.5%
Grade 3	49 50%	56 58.3%
Grade 4	27 27.6%	25 26%
Grade 5	5 5.1%	3 3.1%
Grade 1	2 2%	0 0%
Grade 2	27 27.6%	20 20.8%
Grade 3	41 41.8%	52 54.2%
Grade 4	20 20.4%	21 21.9%
Grade 5	5 5.1%	3 3.1%

5. Secondary Outcome

Title	Health-related Quality of Life (QOL)
Description	Measured by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E). The FACT-E measures multidimensional quality of life in patients with esophagus cancer. Possible scores range from 0 to 68, with higher scores indicating a better outcome.
Time Frame	Baseline, 6 weeks after end of radiation, 1 and 2 years from treatment start

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Quality-adjusted Survival
Time Frame	From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.

Outcome Measure Data

Analysis Population Description

The protocol states that this outcome measure will be analyzed only if primary outcome results are positive, i.e. support the primary hypothesis of this study. Therefore no participants were analyzed for this outcome measure.

Arm/Group Title	Chemoradiation and Trastuzumab	Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	0	0

7. Secondary Outcome

Title	Molecular Correlates of Efficacy
Time Frame	From randomization to last follow-up. Maximum follow-up at time of primary outcome measure analysis was 8 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
Description	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time Frame	From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment

Arm/Group Title	Chemoradiation and Trastuzumab (Arm 1)	Chemoradiation (Arm 2)
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab	Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
Measure Participants	95	96
Count of Participants [Participants]	30 30.6%	24 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation and Trastuzumab (Arm 1), Chemoradiation (Arm 2)
	Comments	Logistic regression was used to model the association of treatment arm (Arm 1 vs. 2 [reference level(RL)]), T stage (T3 vs.T1,T2 [RL]), Zubrod (1,2 vs. 0 [RL]), gender (male vs. female [RL]), presence of adenopathy (yes vs. no [RL]), and age (≥ 60 vs. <60 [RL]) with the occurrence of any cardiac AE, using backwards step-wise model selection requiring p≤0.05 for a covariate to remain in the model. Final model covariates are reported. Age is reported here. No other covariates reported.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.35
	Confidence Interval	(2-Sided) 95%; 1.13 to 4.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Day 8, 15, 22, 29, and 36 and completion (day 57) of concurrent chemoradiation, before surgery (5-8 weeks after last radiation treatment), every 4 mos from the end of surgery for 2 years, then annually until study completion. Maximum follow-up at time of analysis was 8.0 years.
Arm/Group Title	Chemoradiation and Trastuzumab		Chemoradiation
Arm/Group Description	Radiation therapy with concurrent trastuzumab, paclitaxel, and carboplatin followed by surgery followed by maintenance trastuzumab		Radiation therapy with concurrent paclitaxel and carboplatin followed by surgery
All Cause Mortality
	Chemoradiation and Trastuzumab		Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/95 (55.8%)		55/96 (57.3%)
Serious Adverse Events
	Chemoradiation and Trastuzumab		Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/95 (53.7%)		34/96 (35.4%)
Blood and lymphatic system disorders
Anemia	2/95 (2.1%)		2/96 (2.1%)
Febrile neutropenia	3/95 (3.2%)		1/96 (1%)
Leukocytosis	1/95 (1.1%)		0/96 (0%)
Cardiac disorders
Acute coronary syndrome	1/95 (1.1%)		0/96 (0%)
Atrial fibrillation	2/95 (2.1%)		1/96 (1%)
Atrial flutter	1/95 (1.1%)		1/96 (1%)
Cardiac arrest	1/95 (1.1%)		1/96 (1%)
Chest pain - cardiac	2/95 (2.1%)		0/96 (0%)
Pericardial effusion	1/95 (1.1%)		0/96 (0%)
Sinus tachycardia	1/95 (1.1%)		0/96 (0%)
Supraventricular tachycardia	0/95 (0%)		1/96 (1%)
Gastrointestinal disorders
Abdominal pain	2/95 (2.1%)		1/96 (1%)
Bloating	0/95 (0%)		1/96 (1%)
Colonic perforation	0/95 (0%)		1/96 (1%)
Constipation	1/95 (1.1%)		0/96 (0%)
Diarrhea	2/95 (2.1%)		3/96 (3.1%)
Duodenal perforation	0/95 (0%)		1/96 (1%)
Dyspepsia	2/95 (2.1%)		0/96 (0%)
Dysphagia	0/95 (0%)		4/96 (4.2%)
Esophageal fistula	2/95 (2.1%)		0/96 (0%)
Esophageal hemorrhage	1/95 (1.1%)		0/96 (0%)
Esophageal pain	0/95 (0%)		1/96 (1%)
Esophageal perforation	1/95 (1.1%)		0/96 (0%)
Esophageal stenosis	0/95 (0%)		1/96 (1%)
Esophagitis	3/95 (3.2%)		3/96 (3.1%)
Gastric hemorrhage	1/95 (1.1%)		0/96 (0%)
Gastric ulcer	1/95 (1.1%)		0/96 (0%)
Gastrointestinal disorders - Other, specify	2/95 (2.1%)		0/96 (0%)
Ileus	0/95 (0%)		2/96 (2.1%)
Intra-abdominal hemorrhage	1/95 (1.1%)		0/96 (0%)
Malabsorption	1/95 (1.1%)		0/96 (0%)
Nausea	3/95 (3.2%)		6/96 (6.3%)
Obstruction gastric	1/95 (1.1%)		0/96 (0%)
Small intestinal obstruction	1/95 (1.1%)		0/96 (0%)
Vomiting	1/95 (1.1%)		4/96 (4.2%)
General disorders
Chills	1/95 (1.1%)		0/96 (0%)
Death NOS	1/95 (1.1%)		0/96 (0%)
Fatigue	0/95 (0%)		3/96 (3.1%)
Fever	0/95 (0%)		1/96 (1%)
General disorders and administration site conditions - Other, specify	1/95 (1.1%)		0/96 (0%)
Infusion related reaction	1/95 (1.1%)		1/96 (1%)
Multi-organ failure	0/95 (0%)		2/96 (2.1%)
Non-cardiac chest pain	1/95 (1.1%)		0/96 (0%)
Pain	1/95 (1.1%)		1/96 (1%)
Sudden death NOS	1/95 (1.1%)		0/96 (0%)
Hepatobiliary disorders
Hepatic failure	1/95 (1.1%)		0/96 (0%)
Infections and infestations
Catheter related infection	2/95 (2.1%)		1/96 (1%)
Infections and infestations - Other, specify	2/95 (2.1%)		1/96 (1%)
Lung infection	3/95 (3.2%)		3/96 (3.1%)
Pleural infection	1/95 (1.1%)		0/96 (0%)
Sepsis	6/95 (6.3%)		2/96 (2.1%)
Stoma site infection	1/95 (1.1%)		0/96 (0%)
Urinary tract infection	1/95 (1.1%)		1/96 (1%)
Wound infection	1/95 (1.1%)		0/96 (0%)
Injury, poisoning and procedural complications
Esophageal anastomotic leak	3/95 (3.2%)		1/96 (1%)
Gastrointestinal anastomotic leak	0/95 (0%)		1/96 (1%)
Investigations
Cardiac troponin I increased	1/95 (1.1%)		0/96 (0%)
Lymphocyte count decreased	3/95 (3.2%)		4/96 (4.2%)
Neutrophil count decreased	4/95 (4.2%)		3/96 (3.1%)
Platelet count decreased	1/95 (1.1%)		1/96 (1%)
Urine output decreased	1/95 (1.1%)		0/96 (0%)
Weight loss	0/95 (0%)		3/96 (3.1%)
White blood cell decreased	4/95 (4.2%)		5/96 (5.2%)
Metabolism and nutrition disorders
Anorexia	0/95 (0%)		3/96 (3.1%)
Dehydration	5/95 (5.3%)		10/96 (10.4%)
Hyperglycemia	2/95 (2.1%)		0/96 (0%)
Hyperkalemia	1/95 (1.1%)		0/96 (0%)
Hypoglycemia	1/95 (1.1%)		0/96 (0%)
Metabolism and nutrition disorders - Other, specify	0/95 (0%)		1/96 (1%)
Musculoskeletal and connective tissue disorders
Chest wall pain	1/95 (1.1%)		0/96 (0%)
Generalized muscle weakness	1/95 (1.1%)		2/96 (2.1%)
Muscle weakness right-sided	0/95 (0%)		1/96 (1%)
Musculoskeletal and connective tissue disorder - Other, specify	1/95 (1.1%)		0/96 (0%)
Myalgia	0/95 (0%)		1/96 (1%)
Neck pain	1/95 (1.1%)		0/96 (0%)
Nervous system disorders
Cognitive disturbance	1/95 (1.1%)		0/96 (0%)
Headache	1/95 (1.1%)		0/96 (0%)
Seizure	1/95 (1.1%)		1/96 (1%)
Stroke	2/95 (2.1%)		1/96 (1%)
Syncope	1/95 (1.1%)		1/96 (1%)
Psychiatric disorders
Delirium	1/95 (1.1%)		0/96 (0%)
Psychiatric disorders - Other, specify	1/95 (1.1%)		1/96 (1%)
Renal and urinary disorders
Acute kidney injury	2/95 (2.1%)		0/96 (0%)
Hematuria	0/95 (0%)		1/96 (1%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/95 (1.1%)		1/96 (1%)
Aspiration	2/95 (2.1%)		2/96 (2.1%)
Atelectasis	0/95 (0%)		1/96 (1%)
Bronchopleural fistula	1/95 (1.1%)		0/96 (0%)
Chylothorax	1/95 (1.1%)		1/96 (1%)
Dyspnea	1/95 (1.1%)		0/96 (0%)
Epistaxis	1/95 (1.1%)		0/96 (0%)
Pleural effusion	1/95 (1.1%)		1/96 (1%)
Pneumonitis	1/95 (1.1%)		0/96 (0%)
Pneumothorax	1/95 (1.1%)		1/96 (1%)
Productive cough	0/95 (0%)		1/96 (1%)
Pulmonary edema	1/95 (1.1%)		0/96 (0%)
Pulmonary fibrosis	0/95 (0%)		1/96 (1%)
Respiratory failure	2/95 (2.1%)		0/96 (0%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/95 (1.1%)		0/96 (0%)
Tracheal fistula	0/95 (0%)		1/96 (1%)
Skin and subcutaneous tissue disorders
Erythema multiforme	0/95 (0%)		1/96 (1%)
Rash maculo-papular	0/95 (0%)		1/96 (1%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/95 (1.1%)		1/96 (1%)
Vascular disorders
Hypertension	1/95 (1.1%)		0/96 (0%)
Hypotension	5/95 (5.3%)		2/96 (2.1%)
Thromboembolic event	3/95 (3.2%)		2/96 (2.1%)
Visceral arterial ischemia	0/95 (0%)		1/96 (1%)
Other (Not Including Serious) Adverse Events
	Chemoradiation and Trastuzumab		Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/95 (100%)		96/96 (100%)
Blood and lymphatic system disorders
Anemia	61/95 (64.2%)		57/96 (59.4%)
Cardiac disorders
Atrial fibrillation	5/95 (5.3%)		3/96 (3.1%)
Cardiac disorders - Other, specify	3/95 (3.2%)		5/96 (5.2%)
Sinus tachycardia	6/95 (6.3%)		9/96 (9.4%)
Gastrointestinal disorders
Abdominal pain	28/95 (29.5%)		31/96 (32.3%)
Bloating	3/95 (3.2%)		6/96 (6.3%)
Constipation	38/95 (40%)		45/96 (46.9%)
Diarrhea	42/95 (44.2%)		36/96 (37.5%)
Dry mouth	6/95 (6.3%)		7/96 (7.3%)
Dyspepsia	27/95 (28.4%)		16/96 (16.7%)
Dysphagia	57/95 (60%)		50/96 (52.1%)
Esophageal pain	13/95 (13.7%)		13/96 (13.5%)
Esophageal stenosis	8/95 (8.4%)		4/96 (4.2%)
Esophagitis	52/95 (54.7%)		41/96 (42.7%)
Gastritis	7/95 (7.4%)		1/96 (1%)
Gastroesophageal reflux disease	19/95 (20%)		11/96 (11.5%)
Gastrointestinal disorders - Other, specify	13/95 (13.7%)		11/96 (11.5%)
Gastrointestinal pain	6/95 (6.3%)		1/96 (1%)
Mucositis oral	13/95 (13.7%)		14/96 (14.6%)
Nausea	66/95 (69.5%)		69/96 (71.9%)
Vomiting	32/95 (33.7%)		33/96 (34.4%)
General disorders
Chills	12/95 (12.6%)		11/96 (11.5%)
Edema limbs	13/95 (13.7%)		7/96 (7.3%)
Fatigue	78/95 (82.1%)		71/96 (74%)
Fever	12/95 (12.6%)		11/96 (11.5%)
General disorders and administration site conditions - Other, specify	7/95 (7.4%)		2/96 (2.1%)
Infusion related reaction	8/95 (8.4%)		6/96 (6.3%)
Non-cardiac chest pain	8/95 (8.4%)		7/96 (7.3%)
Pain	22/95 (23.2%)		18/96 (18.8%)
Infections and infestations
Lung infection	4/95 (4.2%)		6/96 (6.3%)
Skin infection	3/95 (3.2%)		5/96 (5.2%)
Upper respiratory infection	8/95 (8.4%)		4/96 (4.2%)
Urinary tract infection	5/95 (5.3%)		3/96 (3.1%)
Injury, poisoning and procedural complications
Dermatitis radiation	8/95 (8.4%)		10/96 (10.4%)
Investigations
Alanine aminotransferase increased	10/95 (10.5%)		9/96 (9.4%)
Alkaline phosphatase increased	15/95 (15.8%)		8/96 (8.3%)
Aspartate aminotransferase increased	16/95 (16.8%)		9/96 (9.4%)
Blood bilirubin increased	5/95 (5.3%)		8/96 (8.3%)
Creatinine increased	3/95 (3.2%)		5/96 (5.2%)
Lymphocyte count decreased	40/95 (42.1%)		37/96 (38.5%)
Neutrophil count decreased	47/95 (49.5%)		50/96 (52.1%)
Platelet count decreased	58/95 (61.1%)		64/96 (66.7%)
Weight loss	45/95 (47.4%)		45/96 (46.9%)
White blood cell decreased	78/95 (82.1%)		81/96 (84.4%)
Metabolism and nutrition disorders
Anorexia	41/95 (43.2%)		46/96 (47.9%)
Dehydration	24/95 (25.3%)		22/96 (22.9%)
Hyperglycemia	37/95 (38.9%)		31/96 (32.3%)
Hyperkalemia	6/95 (6.3%)		7/96 (7.3%)
Hypernatremia	6/95 (6.3%)		4/96 (4.2%)
Hypoalbuminemia	26/95 (27.4%)		26/96 (27.1%)
Hypocalcemia	20/95 (21.1%)		19/96 (19.8%)
Hypoglycemia	6/95 (6.3%)		3/96 (3.1%)
Hypokalemia	15/95 (15.8%)		17/96 (17.7%)
Hypomagnesemia	5/95 (5.3%)		11/96 (11.5%)
Hyponatremia	31/95 (32.6%)		24/96 (25%)
Hypophosphatemia	6/95 (6.3%)		5/96 (5.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/95 (7.4%)		3/96 (3.1%)
Back pain	12/95 (12.6%)		18/96 (18.8%)
Generalized muscle weakness	10/95 (10.5%)		10/96 (10.4%)
Myalgia	6/95 (6.3%)		4/96 (4.2%)
Pain in extremity	6/95 (6.3%)		3/96 (3.1%)
Nervous system disorders
Dizziness	20/95 (21.1%)		15/96 (15.6%)
Dysgeusia	13/95 (13.7%)		19/96 (19.8%)
Headache	10/95 (10.5%)		12/96 (12.5%)
Nervous system disorders - Other, specify	6/95 (6.3%)		4/96 (4.2%)
Peripheral sensory neuropathy	17/95 (17.9%)		18/96 (18.8%)
Psychiatric disorders
Anxiety	18/95 (18.9%)		12/96 (12.5%)
Depression	10/95 (10.5%)		10/96 (10.4%)
Insomnia	18/95 (18.9%)		23/96 (24%)
Respiratory, thoracic and mediastinal disorders
Aspiration	2/95 (2.1%)		6/96 (6.3%)
Atelectasis	6/95 (6.3%)		4/96 (4.2%)
Cough	20/95 (21.1%)		24/96 (25%)
Dyspnea	33/95 (34.7%)		21/96 (21.9%)
Epistaxis	6/95 (6.3%)		11/96 (11.5%)
Hiccups	0/95 (0%)		6/96 (6.3%)
Hoarseness	7/95 (7.4%)		7/96 (7.3%)
Pleural effusion	11/95 (11.6%)		8/96 (8.3%)
Pneumothorax	5/95 (5.3%)		4/96 (4.2%)
Productive cough	5/95 (5.3%)		10/96 (10.4%)
Respiratory, thoracic and mediastinal disorders - Other, specify	9/95 (9.5%)		4/96 (4.2%)
Sore throat	8/95 (8.4%)		3/96 (3.1%)
Skin and subcutaneous tissue disorders
Alopecia	10/95 (10.5%)		11/96 (11.5%)
Dry skin	5/95 (5.3%)		5/96 (5.2%)
Pruritus	4/95 (4.2%)		5/96 (5.2%)
Rash maculo-papular	10/95 (10.5%)		14/96 (14.6%)
Skin and subcutaneous tissue disorders - Other, specify	13/95 (13.7%)		2/96 (2.1%)
Vascular disorders
Hypertension	8/95 (8.4%)		15/96 (15.6%)
Hypotension	13/95 (13.7%)		14/96 (14.6%)
Thromboembolic event	2/95 (2.1%)		6/96 (6.3%)

Limitations/Caveats

Due to a considerable decrease in the overall rate of new disease-free survival events, the NRG Data Monitoring Committee (DMC) determined that the study would not reach the required 162 events in a reasonable amount of time. With power from the observed number of events calculated to be greater than 80%, the DMC recommended releasing the results for reporting.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.