Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01015833
• Collaborator: (none)
• Enrollment: 356
• Locations: 673
• Arms: 2
• Actual Duration (Months): 101.9
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies sorafenib tosylate and doxorubicin hydrochloride to see how well they work compared with sorafenib tosylate alone in treating patients with liver cancer that has spread to nearby tissue or lymph nodes or has spread to other places in the body. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sorafenib tosylate together with doxorubicin hydrochloride is more effective than sorafenib tosylate alone in treating liver cancer.

Condition or Disease	Intervention/Treatment	Phase
Advanced Adult Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Unresectable Hepatocellular Carcinoma	Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Drug: Sorafenib Tosylate	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. Compare the overall survival (OS) of patients treated with sorafenib (sorafenib tosylate) and doxorubicin (doxorubicin hydrochloride) to that of those treated with sorafenib.

SECONDARY OBJECTIVES:

1. Compare time to progression (TTP) of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib.

2. Compare progression-free-survival (PFS) of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib.

3. Compare tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib.

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

ARM I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 and sorafenib tosylate orally (PO) once daily (QD) or twice daily (BID) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 356 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized Study of Sorafenib Plus Doxorubicin Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
• Actual Study Start Date: Feb 15, 2010
• Actual Primary Completion Date: May 21, 2015
• Actual Study Completion Date: Aug 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (doxorubicin hydrochloride, sorafenib tosylate) Patients receive doxorubicin hydrochloride IV on day 1 and sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin HCl Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacogenomic Study; Correlative studies; Other Names: PHARMACOGENOMIC ; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib
Experimental: Arm II (sorafenib tosylate) Patients receive sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacogenomic Study; Correlative studies; Other Names: PHARMACOGENOMIC ; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Up to 3 years]

   Overall survival is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.

Secondary Outcome Measures

1. Incidence of Toxicities, as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 3 years]

   Toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.

2. Progression Free Survival [Up to 3 years]

   Progression free survival is defined as the time from study entry to earliest date of disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression).

3. Time to Progression (TTP) [Up to 3 years]

   Time to Progression (TTP) is defined as the time from on study to progression. Progression is defined by the RECIST criteria as Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Median and 95% confidence intervals are provided for each arm below.

4. Best Overall Response Rate [Up to 3 years]

   Best Overall Response Rate is defined as is the best response recorded from the start of the treatment until disease progression/recurrence. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have pathologically or cytologically proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed

• Patients must have locally advanced or metastatic disease; locally advanced disease is defined as disease deemed to be unresectable or non-eligible for transplant without distant metastases

• Lesions must be accurately measurable in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

• No prior adjuvant sorafenib or other v-RAF-1 murine leukemia viral oncogene homolog (Raf)/vascular endothelial growth factor (VEGF) inhibitors; other prior adjuvant therapy is allowed if completed > 6 months prior to registration with documented recurrence of hepatocellular carcinoma (HCC)

• Patients may have been treated with loco regional therapies provided that they either have:

• A target lesion that has not been subjected to local therapy or

• The target lesion(s) within the field of the local therapy has shown an increase of >= 20% in the size since last treatment

• Such therapy must be completed at least 4 weeks prior to registration; patients that have received palliative radiation therapy to the bone need not wait 4 weeks to begin protocol therapy

• Prior therapies allowed include the following:

• Bland embolization, radiation, radioactive microspheres, etc

• Chemoembolization using any chemotherapy (except, see below)

• Chemoembolization drug-eluting beads using doxorubicin

• Prior therapy with chemoembolization using doxorubicin in the non drug eluting beads form is NOT allowed

• No prior systemic therapy for metastatic disease

• No prior exposure to systemic doxorubicin administered intravenously

• Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior to registration

• Allografts are not allowed: no prior history of any allograft, including but not limited to liver and bone marrow transplants

• Patients must have completed any major surgery >= 4 weeks from registration

• Concomitant treatment with Rifampin or St John's wort is not allowed; patients should discontinue these drugs at least 4 weeks prior to registration

• No known central nervous system (CNS) tumors including brain metastases

• No clinically significant gastrointestinal bleeding events requiring intervention, transfusion, or admission to hospital within 30 days prior to registration

• Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on a regimen of anti-hypertensive therapy

• Significant history of cardiac disease is not allowed:

• Congestive heart failure > class II New York Heart Association (NYHA)

• Myocardial infarction within 6 months prior to registration

• Serious myocardial dysfunction, defined as scintigraphically (multigated acquisition scan [MUGA], myocardial scintigram) determined absolute left ventricular ejection fraction (LVEF) below 45% or an LVEF on echocardiogram (ECHO) below the normal limit at the individual institution

• No history of bleeding diathesis

• Patients receiving combination anti-retroviral therapy for human immunodeficiency virus (HIV) are excluded from the study

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Pregnancy/nursing status: women who are pregnant should not go on study; women should not breastfeed while participating in this study

• Granulocytes >= 1,500/uL

• Hemoglobin >= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure patients requiring transfusion prior to registration do not have an occult or clinically apparent gastrointestinal bleed

• Platelets >= 75,000/uL

• Creatinine =< 1.5 x upper limit of normal (ULN) (or creatinine clearance calculated >= 60 cc/minute)

• Child-Pugh score A; patients must meet all laboratory value requirements

• Bilirubin =< 3 mg/dL

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN

• Prothrombin time (PT)-international normalized ratio (INR) =< 1.7 (not required for patients on anticoagulation agents; patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Providence Hospital	Mobile	Alabama	United States	36608
3	Southern Cancer Center PC-Providence	Mobile	Alabama	United States	36608
4	Alaska Regional Hospital	Anchorage	Alaska	United States	99508
5	Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
6	Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas	United States	72401
7	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
8	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
9	PCR Oncology	Arroyo Grande	California	United States	93420
10	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
11	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
12	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
13	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
14	Community Cancer Institute	Clovis	California	United States	93611
15	University Oncology Associates	Clovis	California	United States	93611
16	Epic Care-Dublin	Dublin	California	United States	94568
17	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
18	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
19	Kaiser Permanente-Fontana	Fontana	California	United States	92335
20	Kaiser Permanente-Fremont	Fremont	California	United States	94538
21	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
22	Kaiser Permanente-Fresno	Fresno	California	United States	93720
23	Marin Cancer Care Inc	Greenbrae	California	United States	94904
24	Marin General Hospital	Greenbrae	California	United States	94904
25	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
26	Kaiser Permanente-Irvine	Irvine	California	United States	92618
27	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
28	Kaiser Permanente West Los Angeles	Los Angeles	California	United States	90034
29	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
30	Kaiser Permanente-Modesto	Modesto	California	United States	95356
31	El Camino Hospital	Mountain View	California	United States	94040
32	Highland General Hospital	Oakland	California	United States	94602
33	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
34	Bay Area Tumor Institute	Oakland	California	United States	94609
35	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
36	Tom K Lee Inc	Oakland	California	United States	94609
37	Kaiser Permanente-Oakland	Oakland	California	United States	94611
38	Saint Joseph Hospital - Orange	Orange	California	United States	92868
39	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
40	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
41	East Bay Medical Oncology Hematology Medical Associates Inc-Pleasant Hill	Pleasant Hill	California	United States	94523
42	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
43	Kaiser Permanente-Richmond	Richmond	California	United States	94801
44	Kaiser Permanente-Riverside	Riverside	California	United States	92505
45	Kaiser Permanente-Roseville	Roseville	California	United States	95661
46	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
47	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
48	Salinas Valley Memorial	Salinas	California	United States	93901
49	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
50	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
51	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
52	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
53	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
54	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
55	Kaiser Permanente-San Marcos	San Marcos	California	United States	92078
56	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
57	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
58	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
59	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
60	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
61	Kaiser Permanente-Stockton	Stockton	California	United States	95210
62	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
63	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
64	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
65	Presbyterian Intercommunity Hospital	Whittier	California	United States	90602
66	Kaiser Permanente-Woodland Hills	Woodland Hills	California	United States	91367
67	University of Colorado Hospital	Aurora	Colorado	United States	80045
68	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
69	Valley View Hospital Cancer Center	Glenwood Springs	Colorado	United States	81601
70	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
71	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
72	Kaiser Permanente-Lone Tree	Lone Tree	Colorado	United States	80124
73	Montrose Memorial Hospital	Montrose	Colorado	United States	81401
74	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
75	Middlesex Hospital	Middletown	Connecticut	United States	06457
76	Yale University	New Haven	Connecticut	United States	06520
77	Beebe Medical Center	Lewes	Delaware	United States	19958
78	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
79	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
80	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
81	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
82	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
83	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
84	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
85	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
86	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
87	Veterans Affairs Medical Center -Washington DC	Washington	District of Columbia	United States	20422
88	AdventHealth Altamonte	Altamonte Springs	Florida	United States	32701
89	AdventHealth Kissimmee	Kissimmee	Florida	United States	34744
90	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida	United States	33805
91	AdventHealth Orlando	Orlando	Florida	United States	32803
92	AdventHealth East Orlando	Orlando	Florida	United States	32822
93	Sacred Heart Hospital	Pensacola	Florida	United States	32504
94	AdventHealth Winter Park	Winter Park	Florida	United States	32792
95	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
96	Medical Center of Central Georgia	Macon	Georgia	United States	31201
97	Low Country Cancer Care	Savannah	Georgia	United States	31404
98	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
99	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
100	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
101	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
102	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
103	Queen's Medical Center	Honolulu	Hawaii	United States	96813
104	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
105	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
106	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
107	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
108	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
109	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
110	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
111	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
112	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
113	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
114	Saint Joseph Regional Medical Center	Lewiston	Idaho	United States	83501
115	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
116	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
117	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
118	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
119	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
120	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
121	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
122	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
123	Northwestern University	Chicago	Illinois	United States	60611
124	University of Illinois	Chicago	Illinois	United States	60612
125	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
126	UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital	Chicago	Illinois	United States	60657
127	Carle on Vermilion	Danville	Illinois	United States	61832
128	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
129	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
130	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
131	Crossroads Cancer Center	Effingham	Illinois	United States	62401
132	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
133	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
134	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
135	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
136	Midwest Center for Hematology Oncology	Joliet	Illinois	United States	60432
137	Duly Health and Care Joliet	Joliet	Illinois	United States	60435
138	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
139	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
140	AMITA Health Adventist Medical Center	La Grange	Illinois	United States	60525
141	AMG Libertyville - Oncology	Libertyville	Illinois	United States	60048
142	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
143	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
144	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
145	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
146	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
147	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
148	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
149	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
150	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
151	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
152	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
153	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
154	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
155	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
156	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
157	Valley Radiation Oncology	Peru	Illinois	United States	61354
158	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
159	Swedish American Hospital	Rockford	Illinois	United States	61104
160	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
161	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
162	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
163	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
164	Springfield Clinic	Springfield	Illinois	United States	62702
165	Memorial Medical Center	Springfield	Illinois	United States	62781
166	Carle Cancer Center	Urbana	Illinois	United States	61801
167	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
168	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
169	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
170	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
171	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
172	Elkhart General Hospital	Elkhart	Indiana	United States	46515
173	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
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	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
178	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
179	Cancer Care Partners LLC	Mishawaka	Indiana	United States	46545
180	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
181	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
182	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
183	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
184	Reid Health	Richmond	Indiana	United States	47374
185	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
186	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
187	South Bend Clinic	South Bend	Indiana	United States	46617
188	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
189	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
190	Mary Greeley Medical Center	Ames	Iowa	United States	50010
191	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
192	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
193	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
194	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
195	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
196	Alegent Health Mercy Hospital	Council Bluffs	Iowa	United States	51503
197	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
198	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
199	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa	United States	50501
200	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
201	Iowa City VA Healthcare System	Iowa City	Iowa	United States	52246
202	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
203	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
204	Ottumwa Regional Health Center	Ottumwa	Iowa	United States	52501
205	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
206	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
207	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
208	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
209	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
210	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
211	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
212	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
213	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
214	Providence Medical Center	Kansas City	Kansas	United States	66112
215	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
216	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
217	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
218	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
219	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
220	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
221	Menorah Medical Center	Overland Park	Kansas	United States	66209
222	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
223	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
224	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
225	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
226	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
227	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
228	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
229	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
230	Associates In Womens Health	Wichita	Kansas	United States	67208
231	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
232	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
233	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
234	Wesley Medical Center	Wichita	Kansas	United States	67214
235	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
236	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
237	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
238	Commonwealth Cancer Center-Corbin	Corbin	Kentucky	United States	40701
239	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
240	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
241	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
242	Jewish Hospital	Louisville	Kentucky	United States	40202
243	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky	United States	40215
244	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
245	UofL Health Medical Center Northeast	Louisville	Kentucky	United States	40245
246	Jewish Hospital Medical Center South	Shepherdsville	Kentucky	United States	40165
247	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana	United States	70805
248	Baton Rouge General Medical Center	Baton Rouge	Louisiana	United States	70806
249	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana	United States	70809
250	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana	United States	70809
251	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
252	Ochsner Health Center-Summa	Baton Rouge	Louisiana	United States	70809
253	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana	United States	70809
254	Ochsner Health Center-Covington	Covington	Louisiana	United States	70433
255	Mary Bird Perkins Cancer Center - Houma	Houma	Louisiana	United States	70360
256	West Jefferson Medical Center	Marrero	Louisiana	United States	70072
257	Robert Veith MD LLC	Metairie	Louisiana	United States	70006
258	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
259	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
260	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
261	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
262	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
263	York Hospital	York	Maine	United States	03909
264	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
265	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
266	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
267	Saint Agnes Hospital	Baltimore	Maryland	United States	21229
268	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
269	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
270	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
271	Northwest Hospital Center	Randallstown	Maryland	United States	21133
272	Boston Medical Center	Boston	Massachusetts	United States	02118
273	Bixby Medical Center	Adrian	Michigan	United States	49221
274	Hickman Cancer Center	Adrian	Michigan	United States	49221
275	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
276	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
277	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
278	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
279	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
280	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
281	Hurley Medical Center	Flint	Michigan	United States	48503
282	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
283	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
284	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
285	Allegiance Health	Jackson	Michigan	United States	49201
286	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
287	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
288	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
289	Sparrow Hospital	Lansing	Michigan	United States	48912
290	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
291	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
292	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
293	Lakeland Hospital Niles	Niles	Michigan	United States	49120
294	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
295	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
296	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
297	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
298	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
299	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
300	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
301	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
302	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
303	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
304	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
305	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
306	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
307	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
308	Unity Hospital	Fridley	Minnesota	United States	55432
309	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
310	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
311	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
312	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
313	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
314	Minneapolis VA Medical Center	Minneapolis	Minnesota	United States	55417
315	Health Partners Inc	Minneapolis	Minnesota	United States	55454
316	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
317	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
318	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
319	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
320	Regions Hospital	Saint Paul	Minnesota	United States	55101
321	United Hospital	Saint Paul	Minnesota	United States	55102
322	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
323	Lakeview Hospital	Stillwater	Minnesota	United States	55082
324	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
325	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
326	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
327	Hattiesburg Clinic - Hematology/Oncology Clinic	Hattiesburg	Mississippi	United States	39401
328	Forrest General Hospital / Cancer Center	Hattiesburg	Mississippi	United States	39404
329	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
330	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
331	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
332	Cox Cancer Center Branson	Branson	Missouri	United States	65616
333	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
334	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
335	Veterans Administration	Columbia	Missouri	United States	65201
336	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
337	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
338	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
339	Freeman Health System	Joplin	Missouri	United States	64804
340	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
341	Truman Medical Centers	Kansas City	Missouri	United States	64108
342	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
343	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
344	North Kansas City Hospital	Kansas City	Missouri	United States	64116
345	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
346	Research Medical Center	Kansas City	Missouri	United States	64132
347	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
348	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
349	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
350	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
351	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
352	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
353	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
354	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
355	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
356	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
357	Comprehensive Cancer Care PC	Saint Louis	Missouri	United States	63141
358	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
359	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
360	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
361	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
362	CoxHealth South Hospital	Springfield	Missouri	United States	65807
363	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
364	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
365	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
366	Heartland Hematology and Oncology	Kearney	Nebraska	United States	68845
367	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
368	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
369	Great Plains Health Callahan Cancer Center	North Platte	Nebraska	United States	69101
370	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
371	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
372	Hematology and Oncology Consultants PC	Omaha	Nebraska	United States	68122
373	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
374	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
375	Creighton University Medical Center	Omaha	Nebraska	United States	68131
376	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
377	Midlands Community Hospital	Papillion	Nebraska	United States	68046
378	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
379	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
380	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
381	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
382	GenesisCare USA - Henderson	Henderson	Nevada	United States	89074
383	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
384	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
385	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
386	GenesisCare USA - Las Vegas	Las Vegas	Nevada	United States	89109
387	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
388	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
389	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
390	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
391	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
392	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
393	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada	United States	89128
394	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
395	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
396	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
397	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
398	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
399	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
400	GenesisCare USA - Fort Apache	Las Vegas	Nevada	United States	89148
401	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
402	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
403	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
404	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
405	Renown Regional Medical Center	Reno	Nevada	United States	89502
406	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
407	Radiation Oncology Associates	Reno	Nevada	United States	89509
408	Cancer Care Specialists - Reno	Reno	Nevada	United States	89511
409	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
410	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
411	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
412	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey	United States	08062
413	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07101
414	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
415	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
416	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
417	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York	United States	13021
418	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
419	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
420	James J Peters VA Medical Center	Bronx	New York	United States	10468
421	Veteran Affairs New York Harbor Healthcare System-Brooklyn Campus	Brooklyn	New York	United States	11209
422	Veterans Affairs Western New York Health Care System-Buffalo	Buffalo	New York	United States	14215
423	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
424	Glens Falls Hospital	Glens Falls	New York	United States	12801
425	Northwell Health NCORP	Lake Success	New York	United States	11042
426	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
427	Hematology Oncology Associates of Central New York-Liverpool	Liverpool	New York	United States	13088
428	North Shore University Hospital	Manhasset	New York	United States	11030
429	Garnet Health Medical Center	Middletown	New York	United States	10940
430	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
431	Mount Sinai Union Square	New York	New York	United States	10003
432	Mount Sinai West	New York	New York	United States	10019
433	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
434	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
435	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
436	University of Rochester	Rochester	New York	United States	14642
437	Hematology Oncology Associates of Central New York-Rome	Rome	New York	United States	13440
438	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
439	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
440	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York	United States	13215
441	New York Medical College	Valhalla	New York	United States	10595
442	Mission Hospital	Asheville	North Carolina	United States	28801
443	Mountain Radiation Oncology PA	Asheville	North Carolina	United States	28801
444	AdventHealth Infusion Center Asheville	Asheville	North Carolina	United States	28803
445	Messino Cancer Centers	Asheville	North Carolina	United States	28806
446	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina	United States	28816
447	Transylvania Regional Hospital	Brevard	North Carolina	United States	28712
448	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
449	Sampson Radiation Oncology	Clinton	North Carolina	United States	28328
450	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
451	Angel Medical Center	Franklin	North Carolina	United States	28734
452	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
453	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
454	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
455	AdventHealth Hendersonville	Hendersonville	North Carolina	United States	28792
456	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
457	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
458	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
459	Mission Hospital McDowell	Marion	North Carolina	United States	28752
460	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
461	Blue Ridge Regional Hospital	Spruce Pine	North Carolina	United States	28777
462	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
463	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
464	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
465	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
466	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
467	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
468	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
469	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
470	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
471	Summa Health System - Barberton Campus	Barberton	Ohio	United States	44203
472	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
473	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
474	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
475	Aultman Health Foundation	Canton	Ohio	United States	44710
476	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
477	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
478	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
479	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
480	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
481	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
482	North Coast Cancer Care-Clyde	Clyde	Ohio	United States	43410
483	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
484	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
485	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
486	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
487	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
488	Grant Medical Center	Columbus	Ohio	United States	43215
489	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
490	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
491	Doctors Hospital	Columbus	Ohio	United States	43228
492	Grandview Hospital	Dayton	Ohio	United States	45405
493	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
494	Miami Valley Hospital	Dayton	Ohio	United States	45409
495	Miami Valley Hospital North	Dayton	Ohio	United States	45415
496	Dayton Veterans Affairs Medical Center	Dayton	Ohio	United States	45428
497	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
498	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
499	Grady Memorial Hospital	Delaware	Ohio	United States	43015
500	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
501	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
502	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
503	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
504	Wayne Hospital	Greenville	Ohio	United States	45331
505	Kettering Medical Center	Kettering	Ohio	United States	45429
506	Fairfield Medical Center	Lancaster	Ohio	United States	43130
507	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
508	Saint Rita's Medical Center	Lima	Ohio	United States	45801
509	Lima Memorial Hospital	Lima	Ohio	United States	45804
510	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
511	Saint Luke's Hospital	Maumee	Ohio	United States	43537
512	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
513	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
514	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
515	Licking Memorial Hospital	Newark	Ohio	United States	43055
516	Newark Radiation Oncology	Newark	Ohio	United States	43055
517	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
518	Saint Charles Hospital	Oregon	Ohio	United States	43616
519	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
520	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
521	North Coast Cancer Care	Sandusky	Ohio	United States	44870
522	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
523	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
524	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
525	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
526	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
527	University of Toledo	Toledo	Ohio	United States	43614
528	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
529	Mercy Health - Saint Anne Hospital	Toledo	Ohio	United States	43623
530	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
531	Upper Valley Medical Center	Troy	Ohio	United States	45373
532	Fulton County Health Center	Wauseon	Ohio	United States	43567
533	Saint Ann's Hospital	Westerville	Ohio	United States	43081
534	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
535	Greene Memorial Hospital	Xenia	Ohio	United States	45385
536	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
537	Cancer Care Associates-Norman	Norman	Oklahoma	United States	73071
538	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
539	Mercy Physicians of Oklahoma-Lakeside	Oklahoma City	Oklahoma	United States	73120
540	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
541	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
542	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
543	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
544	Butler Memorial Hospital	Butler	Pennsylvania	United States	16001
545	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240
546	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
547	Reading Hospital	West Reading	Pennsylvania	United States	19611
548	Roger Williams Medical Center	Providence	Rhode Island	United States	02908
549	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
550	AnMed Health Hospital	Anderson	South Carolina	United States	29621
551	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
552	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
553	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
554	Saint Francis Hospital	Greenville	South Carolina	United States	29601
555	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
556	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
557	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
558	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
559	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
560	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
561	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
562	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
563	Carolina Blood and Cancer Care Associates PA-Lancaster	Lancaster	South Carolina	United States	29720
564	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina	United States	29732
565	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
566	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
567	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
568	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
569	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57117-5045
570	Bristol Regional Medical Center	Bristol	Tennessee	United States	37620
571	Wellmont Medical Associates Oncology and Hematology-Bristol	Bristol	Tennessee	United States	37620
572	Memorial Hospital	Chattanooga	Tennessee	United States	37404
573	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee	United States	37343
574	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
575	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee	United States	37660
576	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
577	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
578	Nashville Oncology Associates PC	Nashville	Tennessee	United States	37203
579	Meharry Medical College	Nashville	Tennessee	United States	37208
580	Memorial GYN Plus	Ooltewah	Tennessee	United States	37363
581	The Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
582	Texas Tech University Health Sciences Center-El Paso	El Paso	Texas	United States	79905
583	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
584	Baylor Saint Luke's Medical Center	Houston	Texas	United States	77030
585	Ben Taub General Hospital	Houston	Texas	United States	77030
586	Houston Methodist Hospital	Houston	Texas	United States	77030
587	Michael E DeBakey VA Medical Center	Houston	Texas	United States	77030
588	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
589	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
590	White River Junction Veteran Administration Medical Center	White River Junction	Vermont	United States	05009
591	Danville Regional Medical Center	Danville	Virginia	United States	24541
592	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
593	Sovah Health Martinsville	Martinsville	Virginia	United States	24115
594	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
595	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
596	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
597	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington	United States	98110
598	Overlake Medical Center	Bellevue	Washington	United States	98004
599	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
600	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
601	Harrison Medical Center	Bremerton	Washington	United States	98310
602	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
603	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
604	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
605	Saint Elizabeth Hospital	Enumclaw	Washington	United States	98022
606	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
607	Virginia Mason Federal Way Medical Center	Federal Way	Washington	United States	98002
608	Saint Francis Hospital	Federal Way	Washington	United States	98003
609	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington	United States	98332
610	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington	United States	98335
611	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
612	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
613	Northwest Cancer Clinic	Kennewick	Washington	United States	99336
614	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
615	Saint Clare Hospital	Lakewood	Washington	United States	98499
616	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington	United States	98036
617	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
618	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
619	Capital Medical Center	Olympia	Washington	United States	98507
620	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
621	Peninsula Cancer Center	Poulsbo	Washington	United States	98370
622	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
623	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington	United States	98372
624	Virginia Mason Medical Center	Seattle	Washington	United States	98101
625	Harborview Medical Center	Seattle	Washington	United States	98104
626	Minor and James Medical PLLC	Seattle	Washington	United States	98104
627	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
628	Kaiser Permanente Washington	Seattle	Washington	United States	98112
629	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
630	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
631	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
632	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
633	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
634	Rockwood Clinic	Spokane	Washington	United States	99220
635	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington	United States	97405
636	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington	United States	98405
637	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
638	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
639	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
640	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
641	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
642	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington	United States	98405
643	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
644	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
645	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
646	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
647	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
648	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
649	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
650	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
651	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
652	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
653	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
654	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
655	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
656	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
657	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
658	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
659	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
660	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
661	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
662	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
663	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
664	Grand River Regional Cancer Centre at Grand River Hospital	Kitchener	Ontario	Canada	N2G 1G3
665	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
666	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario	Canada	K1H 8L6
667	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
668	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6
669	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
670	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec	Canada	H3H 2R9
671	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
672	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
673	Fundacion De Investigacion de Diego	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ghassan K Abou-Alfa, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01015833
• Other Study ID Numbers: NCI-2011-01989; NCI-2011-01989; CDR0000659348; CALGB-80802; CALGB-80802; U10CA180821; U10CA031946
• First Posted: Nov 18, 2009
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Doxorubicin; Liposomal doxorubicin; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	180	176
COMPLETED	167	171
NOT COMPLETED	13	5

Baseline Characteristics

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)	Total
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	180	176	356
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62	62
Sex: Female, Male (Count of Participants)
Female	27 15%	23 13.1%	50 14%
Male	153 85%	153 86.9%	306 86%
Region of Enrollment (Count of Participants)
Canada	32 17.8%	29 16.5%	61 17.1%
United States	148 82.2%	147 83.5%	295 82.9%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	180	176
Median (95% Confidence Interval) [month]	8.9	10.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate), Arm II (Sorafenib Tosylate)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Incidence of Toxicities, as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	Toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	180	176
Fatigue	10	7
Hypertension	3	13
White blood cells	11	0
Neutrophils	33	0
Platelets	14	1
Hand Foot Syndrome	10	14

3. Secondary Outcome

Title	Progression Free Survival
Description	Progression free survival is defined as the time from study entry to earliest date of disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression).
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	180	176
Median (95% Confidence Interval) [months]	4.0	3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate), Arm II (Sorafenib Tosylate)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Progression (TTP)
Description	Time to Progression (TTP) is defined as the time from on study to progression. Progression is defined by the RECIST criteria as Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Median and 95% confidence intervals are provided for each arm below.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	180	176
Median (95% Confidence Interval) [months]	4.1	3.8

5. Secondary Outcome

Title	Best Overall Response Rate
Description	Best Overall Response Rate is defined as is the best response recorded from the start of the treatment until disease progression/recurrence. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Patients who started treatment and had follow-up assessments were included in this analysis.

Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)	Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.	Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	150	150
Number [percentage of patients]	7.3	3.3

Adverse Events

Time Frame	Up to 3 years.
Adverse Event Reporting Description	Each CTCAE term is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who completed the study. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.
Arm/Group Title	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)		Arm II (Sorafenib Tosylate)
Arm/Group Description	Patients receive 60 mg/m2 doxorubicin hydrochloride IV on day 1 and 400 mg sorafenib tosylate PO QD or BID on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity.		Patients receive 400 mg sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)		Arm II (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/167 (7.2%)		16/171 (9.4%)
Serious Adverse Events
	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)		Arm II (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/167 (42.5%)		57/171 (33.3%)
Blood and lymphatic system disorders
Anemia	9/167 (5.4%)	10	4/171 (2.3%)	5
Febrile neutropenia	7/167 (4.2%)	8	0/171 (0%)	0
Leukocytosis	1/167 (0.6%)	1	0/171 (0%)	0
Spleen disorder	0/167 (0%)	0	1/171 (0.6%)	1
Thrombotic thrombocytopenic purpura	0/167 (0%)	0	1/171 (0.6%)	1
Cardiac disorders
Atrial fibrillation	3/167 (1.8%)	3	1/171 (0.6%)	1
Cardiac disorder	1/167 (0.6%)	1	0/171 (0%)	0
Chest pain - cardiac	0/167 (0%)	0	1/171 (0.6%)	1
Left ventricular systolic dysfunction	3/167 (1.8%)	3	0/171 (0%)	0
Myocardial infarction	1/167 (0.6%)	1	0/171 (0%)	0
Palpitations	1/167 (0.6%)	1	0/171 (0%)	0
Sinus bradycardia	0/167 (0%)	0	1/171 (0.6%)	1
Sinus tachycardia	1/167 (0.6%)	1	1/171 (0.6%)	1
Endocrine disorders
Hypothyroidism	1/167 (0.6%)	1	1/171 (0.6%)	1
Eye disorders
Conjunctivitis	1/167 (0.6%)	1	0/171 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/167 (0%)	0	1/171 (0.6%)	1
Abdominal pain	22/167 (13.2%)	24	28/171 (16.4%)	33
Anal mucositis	1/167 (0.6%)	1	0/171 (0%)	0
Ascites	3/167 (1.8%)	3	2/171 (1.2%)	2
Colitis	2/167 (1.2%)	2	0/171 (0%)	0
Constipation	1/167 (0.6%)	1	0/171 (0%)	0
Diarrhea	27/167 (16.2%)	28	13/171 (7.6%)	15
Dyspepsia	1/167 (0.6%)	1	0/171 (0%)	0
Dysphagia	3/167 (1.8%)	3	0/171 (0%)	0
Esophageal ulcer	1/167 (0.6%)	2	0/171 (0%)	0
Esophageal varices hemorrhage	1/167 (0.6%)	1	4/171 (2.3%)	4
Esophagitis	2/167 (1.2%)	3	0/171 (0%)	0
Gastric hemorrhage	0/167 (0%)	0	2/171 (1.2%)	2
Gastrointestinal disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Hemorrhoidal hemorrhage	0/167 (0%)	0	1/171 (0.6%)	1
Lower gastrointestinal hemorrhage	1/167 (0.6%)	1	0/171 (0%)	0
Mucositis oral	17/167 (10.2%)	17	4/171 (2.3%)	4
Nausea	34/167 (20.4%)	36	24/171 (14%)	29
Pancreatitis	2/167 (1.2%)	2	0/171 (0%)	0
Rectal hemorrhage	1/167 (0.6%)	1	0/171 (0%)	0
Rectal mucositis	1/167 (0.6%)	1	0/171 (0%)	0
Upper gastrointestinal hemorrhage	1/167 (0.6%)	1	3/171 (1.8%)	4
Vomiting	4/167 (2.4%)	4	6/171 (3.5%)	6
General disorders
Death NOS	4/167 (2.4%)	4	7/171 (4.1%)	7
Edema limbs	1/167 (0.6%)	1	0/171 (0%)	0
Edema trunk	0/167 (0%)	0	1/171 (0.6%)	1
Fatigue	49/167 (29.3%)	56	32/171 (18.7%)	38
Fever	2/167 (1.2%)	2	1/171 (0.6%)	1
Localized edema	0/167 (0%)	0	1/171 (0.6%)	1
Multi-organ failure	1/167 (0.6%)	1	0/171 (0%)	0
Non-cardiac chest pain	0/167 (0%)	0	2/171 (1.2%)	2
Pain	1/167 (0.6%)	1	0/171 (0%)	0
Sudden death NOS	1/167 (0.6%)	1	2/171 (1.2%)	2
Hepatobiliary disorders
Cholecystitis	0/167 (0%)	0	1/171 (0.6%)	1
Gallbladder obstruction	1/167 (0.6%)	1	1/171 (0.6%)	1
Hepatic failure	3/167 (1.8%)	3	1/171 (0.6%)	1
Hepatic hemorrhage	0/167 (0%)	0	2/171 (1.2%)	2
Hepatobiliary disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	2
Immune system disorders
Anaphylaxis	1/167 (0.6%)	1	0/171 (0%)	0
Infections and infestations
Abdominal infection	0/167 (0%)	0	1/171 (0.6%)	1
Bone infection	1/167 (0.6%)	1	1/171 (0.6%)	1
Infections and infestations - Other, specify	3/167 (1.8%)	3	1/171 (0.6%)	1
Lung infection	6/167 (3.6%)	6	0/171 (0%)	0
Peritoneal infection	1/167 (0.6%)	1	1/171 (0.6%)	1
Rash pustular	1/167 (0.6%)	1	0/171 (0%)	0
Sepsis	5/167 (3%)	5	2/171 (1.2%)	2
Skin infection	2/167 (1.2%)	2	2/171 (1.2%)	3
Urinary tract infection	1/167 (0.6%)	1	0/171 (0%)	0
Wound infection	0/167 (0%)	0	1/171 (0.6%)	1
Injury, poisoning and procedural complications
Fall	0/167 (0%)	0	2/171 (1.2%)	2
Fracture	0/167 (0%)	0	1/171 (0.6%)	1
Wound complication	1/167 (0.6%)	1	0/171 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/167 (0%)	0	1/171 (0.6%)	1
Alanine aminotransferase increased	3/167 (1.8%)	3	3/171 (1.8%)	3
Alkaline phosphatase increased	3/167 (1.8%)	3	4/171 (2.3%)	4
Aspartate aminotransferase increased	4/167 (2.4%)	4	6/171 (3.5%)	6
Blood bilirubin increased	8/167 (4.8%)	9	7/171 (4.1%)	7
Creatinine increased	3/167 (1.8%)	3	0/171 (0%)	0
Ejection fraction decreased	3/167 (1.8%)	3	1/171 (0.6%)	1
Haptoglobin decreased	1/167 (0.6%)	1	0/171 (0%)	0
INR increased	2/167 (1.2%)	2	1/171 (0.6%)	1
Leukocyte count decreased	1/167 (0.6%)	1	0/171 (0%)	0
Lipase increased	1/167 (0.6%)	1	0/171 (0%)	0
Lymphocyte count decreased	6/167 (3.6%)	6	2/171 (1.2%)	3
Neutrophil count decreased	31/167 (18.6%)	32	0/171 (0%)	0
Platelet count decreased	35/167 (21%)	38	20/171 (11.7%)	24
Weight loss	2/167 (1.2%)	2	1/171 (0.6%)	1
White blood cell decreased	10/167 (6%)	10	0/171 (0%)	0
Metabolism and nutrition disorders
Anorexia	5/167 (3%)	5	4/171 (2.3%)	4
Dehydration	14/167 (8.4%)	14	5/171 (2.9%)	5
Hyperglycemia	2/167 (1.2%)	2	2/171 (1.2%)	2
Hyperkalemia	4/167 (2.4%)	4	1/171 (0.6%)	1
Hypernatremia	0/167 (0%)	0	1/171 (0.6%)	1
Hypoalbuminemia	4/167 (2.4%)	4	1/171 (0.6%)	1
Hypokalemia	2/167 (1.2%)	2	0/171 (0%)	0
Hypomagnesemia	0/167 (0%)	0	1/171 (0.6%)	1
Hyponatremia	10/167 (6%)	10	4/171 (2.3%)	4
Hypophosphatemia	4/167 (2.4%)	4	1/171 (0.6%)	1
Metabolism and nutrition disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Serum phosphate decreased	1/167 (0.6%)	1	0/171 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/167 (0.6%)	1	1/171 (0.6%)	1
Bone pain	0/167 (0%)	0	1/171 (0.6%)	1
Generalized muscle weakness	1/167 (0.6%)	1	1/171 (0.6%)	1
Myalgia	1/167 (0.6%)	1	0/171 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/167 (0.6%)	1	3/171 (1.8%)	3
Treatment related secondary malignancy	2/167 (1.2%)	2	0/171 (0%)	0
Nervous system disorders
Amnesia	1/167 (0.6%)	1	0/171 (0%)	0
Headache	0/167 (0%)	0	1/171 (0.6%)	1
Intracranial hemorrhage	0/167 (0%)	0	1/171 (0.6%)	1
Nervous system disorders - Other, specify	1/167 (0.6%)	1	0/171 (0%)	0
Seizure	0/167 (0%)	0	1/171 (0.6%)	1
Syncope vasovagal	1/167 (0.6%)	1	0/171 (0%)	0
Psychiatric disorders
Anxiety	1/167 (0.6%)	1	1/171 (0.6%)	1
Confusion	1/167 (0.6%)	1	2/171 (1.2%)	2
Renal and urinary disorders
Acute kidney injury	1/167 (0.6%)	1	0/171 (0%)	0
Hematuria	2/167 (1.2%)	2	1/171 (0.6%)	1
Urogenital disorder	1/167 (0.6%)	1	0/171 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/167 (2.4%)	4	4/171 (2.3%)	4
Epistaxis	1/167 (0.6%)	1	3/171 (1.8%)	3
Hypoxia	1/167 (0.6%)	1	1/171 (0.6%)	1
Pulmonary edema	0/167 (0%)	0	1/171 (0.6%)	1
Sore throat	1/167 (0.6%)	2	0/171 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/167 (1.2%)	2	0/171 (0%)	0
Erythema multiforme	1/167 (0.6%)	1	0/171 (0%)	0
Palmar-plantar erythrodysesthesia syndrome	13/167 (7.8%)	16	10/171 (5.8%)	11
Pruritus	1/167 (0.6%)	1	0/171 (0%)	0
Rash maculo-papular	1/167 (0.6%)	1	2/171 (1.2%)	2
Scalp pain	0/167 (0%)	0	1/171 (0.6%)	1
Skin ulceration	3/167 (1.8%)	3	3/171 (1.8%)	3
Stevens-Johnson syndrome	1/167 (0.6%)	1	0/171 (0%)	0
Vascular disorders
Hypertension	21/167 (12.6%)	25	16/171 (9.4%)	17
Hypotension	2/167 (1.2%)	2	1/171 (0.6%)	1
Thromboembolic event	0/167 (0%)	0	3/171 (1.8%)	3
Other (Not Including Serious) Adverse Events
	Arm I (Doxorubicin Hydrochloride, Sorafenib Tosylate)		Arm II (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/167 (87.4%)		151/171 (88.3%)
Blood and lymphatic system disorders
Anemia	10/167 (6%)	11	8/171 (4.7%)	8
Blood and lymphatic system disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	2
Febrile neutropenia	5/167 (3%)	7	0/171 (0%)	0
Hemoglobin decreased	1/167 (0.6%)	1	0/171 (0%)	0
Hemolysis	1/167 (0.6%)	1	0/171 (0%)	0
Thrombotic thrombocytopenic purpura	1/167 (0.6%)	1	0/171 (0%)	0
Cardiac disorders
Atrial fibrillation	1/167 (0.6%)	5	0/171 (0%)	0
Chest pain - cardiac	0/167 (0%)	0	2/171 (1.2%)	3
Left ventricular failure	0/167 (0%)	0	1/171 (0.6%)	1
Left ventricular systolic dysfunction	7/167 (4.2%)	7	0/171 (0%)	0
Sinus bradycardia	0/167 (0%)	0	1/171 (0.6%)	1
Supraventricular tachycardia	0/167 (0%)	0	1/171 (0.6%)	1
Ventricular tachycardia	0/167 (0%)	0	1/171 (0.6%)	1
Ear and labyrinth disorders
Hearing impaired	0/167 (0%)	0	1/171 (0.6%)	4
Endocrine disorders
Hypothyroidism	5/167 (3%)	14	4/171 (2.3%)	18
Eye disorders
Conjunctivitis	1/167 (0.6%)	1	0/171 (0%)	0
Eye disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Eye pain	0/167 (0%)	0	1/171 (0.6%)	1
Gastrointestinal disorders
Abdominal distension	0/167 (0%)	0	1/171 (0.6%)	1
Abdominal pain	59/167 (35.3%)	156	75/171 (43.9%)	205
Anal fistula	1/167 (0.6%)	1	0/171 (0%)	0
Ascites	3/167 (1.8%)	3	2/171 (1.2%)	2
Bloating	0/167 (0%)	0	1/171 (0.6%)	1
Constipation	1/167 (0.6%)	1	5/171 (2.9%)	6
Dental caries	1/167 (0.6%)	2	0/171 (0%)	0
Diarrhea	68/167 (40.7%)	203	73/171 (42.7%)	256
Dry mouth	0/167 (0%)	0	2/171 (1.2%)	2
Dyspepsia	1/167 (0.6%)	1	0/171 (0%)	0
Esophageal ulcer	1/167 (0.6%)	1	0/171 (0%)	0
Esophageal varices hemorrhage	0/167 (0%)	0	1/171 (0.6%)	2
Esophagitis	2/167 (1.2%)	2	0/171 (0%)	0
Gastroesophageal reflux disease	1/167 (0.6%)	1	0/171 (0%)	0
Hemorrhoids	1/167 (0.6%)	1	0/171 (0%)	0
Mucositis oral	54/167 (32.3%)	126	31/171 (18.1%)	45
Nausea	59/167 (35.3%)	167	64/171 (37.4%)	179
Oral pain	1/167 (0.6%)	1	0/171 (0%)	0
Upper gastrointestinal hemorrhage	0/167 (0%)	0	1/171 (0.6%)	1
Vomiting	5/167 (3%)	5	5/171 (2.9%)	5
General disorders
Chills	0/167 (0%)	0	1/171 (0.6%)	1
Edema limbs	4/167 (2.4%)	6	2/171 (1.2%)	2
Fatigue	111/167 (66.5%)	427	104/171 (60.8%)	407
Fever	1/167 (0.6%)	1	2/171 (1.2%)	2
Gait disturbance	1/167 (0.6%)	1	0/171 (0%)	0
Localized edema	1/167 (0.6%)	1	0/171 (0%)	0
Malaise	1/167 (0.6%)	1	1/171 (0.6%)	2
Non-cardiac chest pain	1/167 (0.6%)	1	0/171 (0%)	0
Pain	4/167 (2.4%)	5	2/171 (1.2%)	2
Hepatobiliary disorders
Hepatic failure	1/167 (0.6%)	1	0/171 (0%)	0
Hepatic hemorrhage	0/167 (0%)	0	1/171 (0.6%)	1
Hepatobiliary disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Infections and infestations
Cecal infection	1/167 (0.6%)	1	0/171 (0%)	0
Gum infection	1/167 (0.6%)	2	0/171 (0%)	0
Lung infection	0/167 (0%)	0	1/171 (0.6%)	1
Papulopustular rash	1/167 (0.6%)	2	1/171 (0.6%)	1
Periorbital infection	1/167 (0.6%)	1	0/171 (0%)	0
Rash pustular	1/167 (0.6%)	1	0/171 (0%)	0
Tooth infection	1/167 (0.6%)	1	0/171 (0%)	0
Upper respiratory infection	0/167 (0%)	0	1/171 (0.6%)	1
Urinary tract infection	2/167 (1.2%)	2	1/171 (0.6%)	2
Injury, poisoning and procedural complications
Dermatitis radiation	1/167 (0.6%)	1	0/171 (0%)	0
Fracture	1/167 (0.6%)	1	1/171 (0.6%)	1
Investigations
Alanine aminotransferase increased	6/167 (3.6%)	7	6/171 (3.5%)	10
Alkaline phosphatase increased	5/167 (3%)	6	9/171 (5.3%)	13
Aspartate aminotransferase increased	12/167 (7.2%)	15	15/171 (8.8%)	25
Blood bilirubin increased	9/167 (5.4%)	10	10/171 (5.8%)	14
CD4 lymphocytes decreased	1/167 (0.6%)	3	0/171 (0%)	0
Creatinine increased	1/167 (0.6%)	1	1/171 (0.6%)	1
Ejection fraction decreased	14/167 (8.4%)	29	0/171 (0%)	0
Electrocardiogram QT corrected interval prolonged	1/167 (0.6%)	1	0/171 (0%)	0
Leukocyte count decreased	3/167 (1.8%)	4	0/171 (0%)	0
Lipase increased	1/167 (0.6%)	1	1/171 (0.6%)	1
Lymphocyte count decreased	8/167 (4.8%)	15	9/171 (5.3%)	20
Neutrophil count decreased	58/167 (34.7%)	110	11/171 (6.4%)	69
Platelet count decreased	67/167 (40.1%)	199	62/171 (36.3%)	348
Weight loss	1/167 (0.6%)	1	4/171 (2.3%)	6
White blood cell decreased	11/167 (6.6%)	13	1/171 (0.6%)	1
Metabolism and nutrition disorders
Anorexia	6/167 (3.6%)	8	11/171 (6.4%)	16
Blood glucose increased	0/167 (0%)	0	1/171 (0.6%)	1
Dehydration	1/167 (0.6%)	1	2/171 (1.2%)	3
Hypercalcemia	1/167 (0.6%)	1	0/171 (0%)	0
Hyperglycemia	9/167 (5.4%)	12	9/171 (5.3%)	11
Hyperkalemia	1/167 (0.6%)	1	1/171 (0.6%)	1
Hypermagnesemia	1/167 (0.6%)	3	0/171 (0%)	0
Hypernatremia	0/167 (0%)	0	1/171 (0.6%)	1
Hyperuricemia	1/167 (0.6%)	2	0/171 (0%)	0
Hypoalbuminemia	2/167 (1.2%)	2	2/171 (1.2%)	3
Hypocalcemia	1/167 (0.6%)	1	0/171 (0%)	0
Hypoglycemia	1/167 (0.6%)	1	1/171 (0.6%)	1
Hypokalemia	3/167 (1.8%)	7	2/171 (1.2%)	2
Hypomagnesemia	3/167 (1.8%)	3	0/171 (0%)	0
Hyponatremia	7/167 (4.2%)	13	11/171 (6.4%)	16
Hypophosphatemia	6/167 (3.6%)	15	11/171 (6.4%)	16
Metabolism and nutrition disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Serum albumin decreased	2/167 (1.2%)	2	0/171 (0%)	0
Serum phosphate decreased	1/167 (0.6%)	1	0/171 (0%)	0
Serum potassium decreased	1/167 (0.6%)	1	0/171 (0%)	0
Serum sodium decreased	0/167 (0%)	0	1/171 (0.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/167 (0.6%)	1	0/171 (0%)	0
Arthritis	1/167 (0.6%)	1	0/171 (0%)	0
Back pain	0/167 (0%)	0	3/171 (1.8%)	7
Chest wall pain	1/167 (0.6%)	1	0/171 (0%)	0
Generalized muscle weakness	2/167 (1.2%)	2	1/171 (0.6%)	1
Muscle weakness upper limb	1/167 (0.6%)	1	0/171 (0%)	0
Musculoskeletal disorder	1/167 (0.6%)	1	0/171 (0%)	0
Myalgia	0/167 (0%)	0	1/171 (0.6%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/167 (0%)	0	1/171 (0.6%)	5
Nervous system disorders
Dysgeusia	0/167 (0%)	0	1/171 (0.6%)	1
Encephalopathy	1/167 (0.6%)	1	0/171 (0%)	0
Headache	1/167 (0.6%)	2	1/171 (0.6%)	1
Paresthesia	1/167 (0.6%)	1	0/171 (0%)	0
Peripheral sensory neuropathy	1/167 (0.6%)	1	2/171 (1.2%)	3
Psychiatric disorders
Confusion	0/167 (0%)	0	2/171 (1.2%)	2
Depression	2/167 (1.2%)	2	2/171 (1.2%)	3
Insomnia	2/167 (1.2%)	2	2/171 (1.2%)	2
Renal and urinary disorders
Chronic kidney disease	0/167 (0%)	0	1/171 (0.6%)	1
Hematuria	5/167 (3%)	10	4/171 (2.3%)	5
Respiratory, thoracic and mediastinal disorders
Cough	1/167 (0.6%)	2	0/171 (0%)	0
Dyspnea	1/167 (0.6%)	1	6/171 (3.5%)	8
Epistaxis	7/167 (4.2%)	8	12/171 (7%)	16
Hiccups	0/167 (0%)	0	1/171 (0.6%)	1
Hypoxia	1/167 (0.6%)	2	0/171 (0%)	0
Sore throat	1/167 (0.6%)	1	0/171 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	3/167 (1.8%)	5	1/171 (0.6%)	2
Dry skin	0/167 (0%)	0	3/171 (1.8%)	5
Erythema multiforme	0/167 (0%)	0	1/171 (0.6%)	1
Hand-and-foot syndrome	0/167 (0%)	0	1/171 (0.6%)	1
Nail discoloration	1/167 (0.6%)	2	0/171 (0%)	0
Palmar-plantar erythrodysesthesia syndrome	57/167 (34.1%)	197	68/171 (39.8%)	215
Pruritus	1/167 (0.6%)	1	0/171 (0%)	0
Rash acneiform	1/167 (0.6%)	1	0/171 (0%)	0
Rash maculo-papular	6/167 (3.6%)	7	3/171 (1.8%)	3
Scalp pain	0/167 (0%)	0	1/171 (0.6%)	1
Skin and subcutaneous tissue disorders - Other, specify	0/167 (0%)	0	1/171 (0.6%)	1
Skin disorder	0/167 (0%)	0	1/171 (0.6%)	3
Skin ulceration	8/167 (4.8%)	16	7/171 (4.1%)	9
Vascular disorders
Flushing	0/167 (0%)	0	1/171 (0.6%)	1
Hypertension	49/167 (29.3%)	172	68/171 (39.8%)	316
Hypotension	1/167 (0.6%)	1	1/171 (0.6%)	1
Thromboembolic event	3/167 (1.8%)	15	0/171 (0%)	0
Thrombosis	1/167 (0.6%)	1	0/171 (0%)	0

Limitations/Caveats

[Not Specified]

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.