Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01198158
• Collaborator: (none)
• Enrollment: 77
• Locations: 524
• Arms: 2
• Actual Duration (Months): 87
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7	Biological: Bevacizumab; Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) treatment.

SECONDARY OBJECTIVES:

1. To compare the progression-free survival and proportion who experience an objective response (defined as complete clinical response [cCR] + partial response [PR]) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone.

2. To compare grade 3 or higher toxicity in patients receiving each treatment regimen.

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

ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive everolimus PO QD on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial Comparing Everolimus Versus Everolimus Plus Bevacizumab for Advanced Renal Cell Carcinoma Progressing After Treatment With Tyrosine Kinase Inhibitors
• Actual Study Start Date: Sep 15, 2010
• Actual Primary Completion Date: Dec 15, 2017
• Actual Study Completion Date: Dec 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (everolimus) Patients receive everolimus PO QD on days 1-28.	Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin Afinitor Certican RAD 001 RAD001 Votubia Zortress ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies
Experimental: Arm II (everolimus with bevacizumab) Patients receive everolimus PO QD on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15.	Biological: Bevacizumab; Given IV; Other Names: Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF rhuMAb Avastin Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar QL 1101 BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF ; Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin Afinitor Certican RAD 001 RAD001 Votubia Zortress ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [The time from date of randomization to date of death due to any cause, assessed up to 5.5 years]

   Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [The time from randomization to disease progression or death from any cause, assessed up to 5.5 years]

   Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

2. Objective Response Rate (CR + PR) [Up to 5.5 years]

   The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.

3. Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after completion of study treatment]

   The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Renal cell carcinoma with some component of clear cell histology

• Metastatic or unresectable disease

• Must have been treated with at least 1 prior VEGFR tyrosine kinase inhibitor treatment and have progressed or have been intolerant to treatment

• No prior systemic therapy with a vascular endothelial growth factor (VEGF) binding agent (e.g., bevacizumab)

• No prior systemic therapy with any mechanistic target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)

• Prior cytokine therapy is allowed

• Any systemic therapy must be completed at least 4 weeks prior to registration

• = 2 weeks since any prior radiation (including palliative)

• Patients must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study registration, and must have fully recovered from any such procedure

• The following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies and routine dental procedures

• Patients must have measurable disease by RECIST criteria; lesions that can be accurately measured 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 active brain metastases: patients with treated, stable brain metastases for at least three months are eligible as long as they meet the following criteria:

• Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 are not eligible

• Baseline brain imaging (MRI/CT) is required

• No serious non-healing wound, ulcer, or bone fracture

• No arterial thrombotic events within 6 months of registration:

• Including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection), or any other arterial thrombotic event are ineligible

• Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study

• Patients receiving anti-platelet agents and prophylactic anticoagulation are eligible

• No inadequately controlled hypertension: (defined as a blood pressure of >= 160 mmHg systolic and/or >= 90 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy

• No known severe impairment of lung function, defined as >= grade 2 dyspnea or cough, or either:

• Requirement of supplemental oxygen, or

• In cases where pulmonary function or pulse oximetry tests have been obtained, forced expiratory volume of the lung in one second (FEV1) or forced vital capacity (FVC) are < 50% of predicted, or single breath diffusing capacity of the lung for carbon monoxide (DLCO) is < 35% of predicted or resting room oxygen saturation is less than 90%

• No active or severe liver disease (e.g. acute or chronic hepatitis, cirrhosis)

• No positive serology for anti-hemoglobin C (HBC) or anti-hepatitis C virus (HCV) antibodies; hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen [HBsAg] positive) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxryribonucleic acid (DNA) testing and agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus

• No New York Heart Association (NYHA) class >= 2 congestive heart failure

• No active bleeding or chronic hemorrhagic diathesis or increased risk for bleeding: Including but not limited to history of major bleeding within 6 months (e.g. gastrointestinal, lung, CNS sites; or required transfusion support)

• No history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to the initiation of treatment

• No ongoing immunosuppressive therapy: including chronic systemic treatment with corticosteroids (>= 10 mg/day prednisone equivalent)

• Archival tissue must be available for submission: though it is optional patients to choose to participate in the correlative substudies or not

• Patients who are pregnant or nursing are not eligible

• Women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration

• Women of child-bearing potential include:

• Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)

• Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL

• Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)

• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky score >= 60%

• Granulocytes >= 1,500/μL

• Platelet count >= 100,000/μL

• Calculated creatinine clearance >= 30 mL/minute (modified Cockroft and Gault formula)

• Bilirubin =< 1.5 x upper limits of normal

• Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN)

• Fasting serum triglycerides =< 200 mg/dL

• Serum cholesterol =< 300 mg/dL

• Fasting serum glucose =< 1.5 x ULN

• Urine protein to creatinine ratio < 1.0 or urine protein =< 1+

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
5	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
6	PCR Oncology	Arroyo Grande	California	United States	93420
7	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
8	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
9	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
10	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
11	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
12	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
13	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
14	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
15	Kaiser Permanente-Fontana	Fontana	California	United States	92335
16	Kaiser Permanente-Fremont	Fremont	California	United States	94538
17	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
18	Kaiser Permanente-Fresno	Fresno	California	United States	93720
19	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
20	Kaiser Permanente-Irvine	Irvine	California	United States	92618
21	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
22	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
23	Kaiser Permanente-Cadillac	Los Angeles	California	United States	90034
24	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
25	Memorial Medical Center	Modesto	California	United States	95355
26	El Camino Hospital	Mountain View	California	United States	94040
27	Sutter Cancer Research Consortium	Novato	California	United States	94945
28	Highland General Hospital	Oakland	California	United States	94602
29	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
30	Bay Area Tumor Institute	Oakland	California	United States	94609
31	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
32	Tom K Lee Inc	Oakland	California	United States	94609
33	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
34	Kaiser Permanente-Oakland	Oakland	California	United States	94611
35	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
36	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
37	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
38	Kaiser Permanente-Richmond	Richmond	California	United States	94801
39	Kaiser Permanente-Riverside	Riverside	California	United States	92505
40	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
41	Kaiser Permanente-Roseville	Roseville	California	United States	95661
42	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
43	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
44	South Sacramento Cancer Center	Sacramento	California	United States	95823
45	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
46	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
47	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
48	Zuckerberg San Francisco General Hospital	San Francisco	California	United States	94110
49	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
50	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
51	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
52	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
53	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
54	Kaiser Permanente-San Marcos	San Marcos	California	United States	92078
55	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
56	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
57	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
58	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
59	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
60	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
61	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
62	Kaiser Permanente-Stockton	Stockton	California	United States	95210
63	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
64	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
65	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
66	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
67	Kaiser Permanente-Woodland Hills	Woodland Hills	California	United States	91367
68	The Medical Center of Aurora	Aurora	Colorado	United States	80012
69	Boulder Community Hospital	Boulder	Colorado	United States	80301
70	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
71	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
72	Porter Adventist Hospital	Denver	Colorado	United States	80210
73	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
74	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
75	Rose Medical Center	Denver	Colorado	United States	80220
76	Colorado Cancer Research Program NCORP	Denver	Colorado	United States	80222
77	Swedish Medical Center	Englewood	Colorado	United States	80113
78	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
79	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
80	North Colorado Medical Center	Greeley	Colorado	United States	80631
81	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
82	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
83	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
84	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
85	Longmont United Hospital	Longmont	Colorado	United States	80501
86	McKee Medical Center	Loveland	Colorado	United States	80539
87	Parker Adventist Hospital	Parker	Colorado	United States	80138
88	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
89	North Suburban Medical Center	Thornton	Colorado	United States	80229
90	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
91	Hartford Hospital	Hartford	Connecticut	United States	06102
92	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
93	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
94	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut	United States	06904
95	Beebe Medical Center	Lewes	Delaware	United States	19958
96	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
97	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
98	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
99	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
100	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
101	Jupiter Medical Center	Jupiter	Florida	United States	33458
102	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
103	21st Century Oncology-Orange Park	Orange Park	Florida	United States	32073
104	Florida Hospital Orlando	Orlando	Florida	United States	32803
105	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
106	Sacred Heart Hospital	Pensacola	Florida	United States	32504
107	Cleveland Clinic-Weston	Weston	Florida	United States	33331
108	Phoebe Putney Memorial Hospital	Albany	Georgia	United States	31701
109	Medical Center of Central Georgia	Macon	Georgia	United States	31201
110	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
111	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
112	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii	United States	96813
113	Queen's Medical Center	Honolulu	Hawaii	United States	96813
114	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
115	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
116	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii	United States	96817
117	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
118	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
119	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
120	Castle Medical Center	Kailua	Hawaii	United States	96734
121	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
122	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
123	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
124	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
125	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
126	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
127	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
128	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
129	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
130	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
131	Graham Hospital Association	Canton	Illinois	United States	61520
132	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
133	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
134	Memorial Hospital	Carthage	Illinois	United States	62321
135	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois	United States	60612
136	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
137	University of Illinois	Chicago	Illinois	United States	60612
138	Presence Resurrection Medical Center	Chicago	Illinois	United States	60631
139	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
140	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
141	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
142	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
143	Eureka Hospital	Eureka	Illinois	United States	61530
144	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
145	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
146	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
147	Mason District Hospital	Havana	Illinois	United States	62644
148	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
149	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
150	AMITA Health Adventist Medical Center	La Grange	Illinois	United States	60525
151	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
152	Mcdonough District Hospital	Macomb	Illinois	United States	61455
153	Loyola University Medical Center	Maywood	Illinois	United States	60153
154	Holy Family Medical Center	Monmouth	Illinois	United States	61462
155	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
156	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
157	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
158	Community Cancer Center Foundation	Normal	Illinois	United States	61761
159	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
160	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
161	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
162	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
163	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
164	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
165	Proctor Hospital	Peoria	Illinois	United States	61614
166	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
167	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
168	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
169	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
170	Illinois Valley Hospital	Peru	Illinois	United States	61354
171	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
172	Perry Memorial Hospital	Princeton	Illinois	United States	61356
173	West Suburban Medical Center	River Forest	Illinois	United States	60305
174	Swedish American Hospital	Rockford	Illinois	United States	61104
175	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
176	Memorial Medical Center	Springfield	Illinois	United States	62781
177	Carle Cancer Center	Urbana	Illinois	United States	61801
178	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
179	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
180	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
181	Elkhart General Hospital	Elkhart	Indiana	United States	46515
182	Radiation Oncology Associates PC	Fort Wayne	Indiana	United States	46804
183	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
184	Franciscan Health Indianapolis	Indianapolis	Indiana	United States	46237
185	Community Howard Regional Health	Kokomo	Indiana	United States	46904
186	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
187	Premier Oncology Hematology Associates	Merrillville	Indiana	United States	46410
188	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
189	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
190	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
191	Reid Health	Richmond	Indiana	United States	47374
192	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
193	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
194	South Bend Clinic	South Bend	Indiana	United States	46617
195	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
196	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
197	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
198	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa	United States	52402
199	Saint Luke's Hospital	Cedar Rapids	Iowa	United States	52402
200	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
201	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
202	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
203	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
204	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
205	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
206	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
207	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
208	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
209	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
210	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
211	Iowa City VA Healthcare System	Iowa City	Iowa	United States	52246
212	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
213	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
214	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
215	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
216	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
217	Providence Medical Center	Kansas City	Kansas	United States	66112
218	Menorah Medical Center	Overland Park	Kansas	United States	66209
219	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
220	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
221	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas	United States	66204
222	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
223	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
224	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
225	University Health-Conway	Monroe	Louisiana	United States	71202
226	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
227	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
228	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
229	Highland Clinic	Shreveport	Louisiana	United States	71105
230	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
231	Eastern Maine Medical Center	Bangor	Maine	United States	04401
232	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
233	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
234	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
235	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
236	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
237	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
238	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
239	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135
240	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
241	Berkshire Hematology Oncology PC	Pittsfield	Massachusetts	United States	01201
242	Baystate Medical Center	Springfield	Massachusetts	United States	01199
243	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
244	Bixby Medical Center	Adrian	Michigan	United States	49221
245	Hickman Cancer Center	Adrian	Michigan	United States	49221
246	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
247	McLaren Cancer Institute-Bay City	Bay City	Michigan	United States	48706
248	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
249	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
250	Henry Ford Hospital	Detroit	Michigan	United States	48202
251	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
252	McLaren Cancer Institute-Flint	Flint	Michigan	United States	48532
253	Singh and Arora Hematology Oncology PC	Flint	Michigan	United States	48532
254	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
255	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
256	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
257	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
258	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
259	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
260	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
261	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan	United States	48446
262	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
263	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
264	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan	United States	48043
265	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
266	Lakeland Hospital Niles	Niles	Michigan	United States	49120
267	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan	United States	49770
268	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
269	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
270	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
271	Munson Medical Center	Traverse City	Michigan	United States	49684
272	Metro Health Hospital	Wyoming	Michigan	United States	49519
273	Medini, Eitan MD (UIA Investigator)	Alexandria	Minnesota	United States	56308
274	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
275	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
276	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
277	Unity Hospital	Fridley	Minnesota	United States	55432
278	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
279	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
280	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
281	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
282	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
283	Minneapolis Veterans Medical Center	Minneapolis	Minnesota	United States	55417
284	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
285	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
286	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
287	Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
288	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
289	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
290	Regions Hospital	Saint Paul	Minnesota	United States	55101
291	United Hospital	Saint Paul	Minnesota	United States	55102
292	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
293	Lakeview Hospital	Stillwater	Minnesota	United States	55082
294	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
295	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
296	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
297	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
298	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
299	Cox Cancer Center Branson	Branson	Missouri	United States	65616
300	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
301	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
302	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
303	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
304	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
305	Freeman Health System	Joplin	Missouri	United States	64804
306	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
307	Truman Medical Center	Kansas City	Missouri	United States	64108
308	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
309	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
310	North Kansas City Hospital	Kansas City	Missouri	United States	64116
311	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
312	Research Medical Center	Kansas City	Missouri	United States	64132
313	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
314	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
315	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
316	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
317	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64507
318	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
319	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
320	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
321	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
322	Comprehensive Cancer Care PC	Saint Louis	Missouri	United States	63141
323	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
324	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
325	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
326	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
327	CoxHealth South Hospital	Springfield	Missouri	United States	65807
328	Billings Clinic Cancer Center	Billings	Montana	United States	59101
329	Saint Vincent Healthcare	Billings	Montana	United States	59101
330	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
331	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
332	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
333	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
334	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
335	Big Sky Oncology	Great Falls	Montana	United States	59405
336	Great Falls Clinic	Great Falls	Montana	United States	59405
337	Northern Montana Hospital	Havre	Montana	United States	59501
338	Saint Peter's Community Hospital	Helena	Montana	United States	59601
339	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
340	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
341	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
342	Montana Cancer Specialists	Missoula	Montana	United States	59802
343	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
344	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
345	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
346	Great Plains Health Callahan Cancer Center	North Platte	Nebraska	United States	69101
347	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
348	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
349	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
350	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
351	Virtua Memorial	Mount Holly	New Jersey	United States	08060
352	Virtua Voorhees	Voorhees	New Jersey	United States	08043
353	Veterans Affairs Western New York Health Care System-Buffalo	Buffalo	New York	United States	14215
354	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
355	Glens Falls Hospital	Glens Falls	New York	United States	12801
356	Orange Regional Medical Center	Middletown	New York	United States	10940
357	Weill Medical College of Cornell University	New York	New York	United States	10065
358	Staten Island University Hospital	Staten Island	New York	United States	10305
359	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
360	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina	United States	28801
361	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
362	Carolinas HealthCare System NorthEast	Concord	North Carolina	United States	28025
363	Duke University Medical Center	Durham	North Carolina	United States	27710
364	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
365	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
366	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
367	Marion L Shepard Cancer Center at Vidant Beaufort Hospital	Washington	North Carolina	United States	27889
368	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
369	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
370	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
371	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
372	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
373	Summa Barberton Hospital	Barberton	Ohio	United States	44203
374	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
375	Mercy Medical Center	Canton	Ohio	United States	44708
376	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
377	North Coast Cancer Care-Clyde	Clyde	Ohio	United States	43410
378	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
379	Grandview Hospital	Dayton	Ohio	United States	45405
380	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
381	Miami Valley Hospital	Dayton	Ohio	United States	45409
382	Samaritan North Health Center	Dayton	Ohio	United States	45415
383	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
384	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
385	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
386	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
387	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
388	Wayne Hospital	Greenville	Ohio	United States	45331
389	Kettering Medical Center	Kettering	Ohio	United States	45429
390	Saint Rita's Medical Center	Lima	Ohio	United States	45801
391	Lima Memorial Hospital	Lima	Ohio	United States	45804
392	Saint Luke's Hospital	Maumee	Ohio	United States	43537
393	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
394	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
395	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
396	Saint Charles Hospital	Oregon	Ohio	United States	43616
397	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
398	North Coast Cancer Care	Sandusky	Ohio	United States	44870
399	ProMedica Flower Hospital	Sylvania	Ohio	United States	43560
400	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
401	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
402	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
403	University of Toledo	Toledo	Ohio	United States	43614
404	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
405	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
406	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
407	Upper Valley Medical Center	Troy	Ohio	United States	45373
408	Fulton County Health Center	Wauseon	Ohio	United States	43567
409	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
410	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
411	Greene Memorial Hospital	Xenia	Ohio	United States	45385
412	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
413	Cancer Care Associates-Norman	Norman	Oklahoma	United States	73071
414	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
415	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
416	Mercy Physicians of Oklahoma-Lakeside	Oklahoma City	Oklahoma	United States	73120
417	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
418	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
419	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
420	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
421	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
422	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
423	Providence Portland Medical Center	Portland	Oregon	United States	97213
424	Adventist Medical Center	Portland	Oregon	United States	97216
425	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
426	Compass Oncology Rose Quarter	Portland	Oregon	United States	97227
427	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
428	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
429	Mid-Columbia Medical Center/Celilo Cancer Center	The Dalles	Oregon	United States	97058
430	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
431	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
432	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
433	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
434	Butler Memorial Hospital	Butler	Pennsylvania	United States	16001
435	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
436	Ephrata Cancer Center	Ephrata	Pennsylvania	United States	17522
437	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
438	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
439	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
440	Riddle Memorial Hospital	Media	Pennsylvania	United States	19063
441	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
442	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
443	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania	United States	18508
444	Geisinger Medical Group	State College	Pennsylvania	United States	16801
445	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
446	Associates In Hematology Oncology PC-Upland	Upland	Pennsylvania	United States	19013
447	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
448	UPMC Susquehanna	Williamsport	Pennsylvania	United States	17701
449	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
450	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
451	Roper Hospital	Charleston	South Carolina	United States	29401
452	Greenville Health System Cancer Institute-Easley	Easley	South Carolina	United States	29640
453	Saint Francis Hospital	Greenville	South Carolina	United States	29601
454	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina	United States	29605
455	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
456	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
457	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
458	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
459	Greenville Health System Cancer Institute-Greer	Greer	South Carolina	United States	29650
460	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina	United States	29672
461	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
462	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
463	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57105
464	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
465	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
466	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
467	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
468	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
469	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
470	White River Junction Veteran Administration Medical Center	White River Junction	Vermont	United States	05009
471	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
472	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia	United States	24501
473	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
474	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
475	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
476	Saint Francis Hospital	Federal Way	Washington	United States	98003
477	Saint Clare Hospital	Lakewood	Washington	United States	98499
478	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
479	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
480	Rockwood Clinic	Spokane	Washington	United States	99220
481	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
482	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
483	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
484	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
485	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
486	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
487	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
488	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
489	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701
490	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
491	Fox Valley Hematology and Oncology SC-Appleton	Appleton	Wisconsin	United States	54913
492	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
493	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
494	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
495	Aurora Cancer Care-Franklin	Franklin	Wisconsin	United States	53132
496	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
497	Aurora Cancer Care-Glendale	Glendale	Wisconsin	United States	53212
498	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
499	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
500	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
501	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
502	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
503	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
504	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
505	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
506	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
507	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
508	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
509	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
510	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
511	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
512	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
513	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
514	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
515	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
516	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
517	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
518	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
519	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
520	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
521	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin	United States	54494
522	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
523	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
524	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: George Philips, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 1, 2014

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01198158
• Other Study ID Numbers: NCI-2011-02603; NCI-2011-02603; CDR0000684313; CALGB 90802; CALGB-90802; U10CA180821; U10CA031946
• First Posted: Sep 9, 2010
• Last Update Posted: Mar 6, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Bevacizumab; Antineoplastic Agents, Immunological; Everolimus; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G

Study Results

Participant Flow

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
Period Title: Overall Study
STARTED	41	36
COMPLETED	41	36
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)	Total
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.	Total of all reporting groups
Overall Participants	41	36	77
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.9	62	62.2
Sex: Female, Male (Count of Participants)
Female	13 31.7%	5 13.9%	18 23.4%
Male	28 68.3%	31 86.1%	59 76.6%
Race/Ethnicity, Customized (Count of Participants)
White	35 85.4%	32 88.9%	67 87%
Non-White	6 14.6%	4 11.1%	10 13%
Region of Enrollment (Count of Participants)
United States	41 100%	36 100%	77 100%
Dominant clear cell histology (Count of Participants)
Count of Participants [Participants]	34 82.9%	30 83.3%	64 83.1%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	The time from date of randomization to date of death due to any cause, assessed up to 5.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
Measure Participants	41	36
Median (95% Confidence Interval) [months]	27.5	21.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Everolimus), Arm II (Everolimus With Bevacizumab)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.739
	Comments
	Method	Log Rank
	Comments	OS was analyzed based on an intent-to-treat approach using the stratified log-rank statistic adjusting on the stratification factors.

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	The time from randomization to disease progression or death from any cause, assessed up to 5.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
Measure Participants	41	36
Median (95% Confidence Interval) [months]	7.2	6.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Everolimus), Arm II (Everolimus With Bevacizumab)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	Log Rank
	Comments	PFS was analyzed based on an intent-to-treat approach using the stratified log-rank statistic adjusting on the stratification factors

3. Secondary Outcome

Title	Objective Response Rate (CR + PR)
Description	The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
Time Frame	Up to 5.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
Measure Participants	41	36
Number (95% Confidence Interval) [percentage of participants]	17.1 41.7%	16.7 46.4%

4. Secondary Outcome

Title	Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.
Time Frame	Up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

All patients that started protocol treatment and were assessed for adverse events were included in this endpoint.

Arm/Group Title	Arm I (Everolimus)	Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.	Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
Measure Participants	38	33
Grade 3 Adverse event	21 51.2%	20 55.6%
Grade 4 Adverse event	1 2.4%	3 8.3%

Adverse Events

Time Frame	Up to 30 days after completion of study treatment
Adverse Event Reporting Description	Each CTCAE term is a unique representation of a specific event used for medical documentation & scientific analysis & is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients with at least 1 cycle of tx and 1 AE form. Serious AE (SAE) reports may include any secondary serious/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, & appear in the SAE table.
Arm/Group Title	Arm I (Everolimus)		Arm II (Everolimus With Bevacizumab)
Arm/Group Description	Patients receive everolimus 10mg daily orally plus intravenous placebo on day 1 and 15 (control arm) in a 28 day cycle.		Patients receive everolimus 10mg daily orally plus intravenous bevacizumab 10mg/kg intravenously on day 1 and 15 (experimental arm) in a 28 day cycle.
All Cause Mortality
	Arm I (Everolimus)		Arm II (Everolimus With Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/41 (80.5%)		28/36 (77.8%)
Serious Adverse Events
	Arm I (Everolimus)		Arm II (Everolimus With Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/38 (23.7%)		11/33 (33.3%)
Blood and lymphatic system disorders
Anemia	6/38 (15.8%)	6	8/33 (24.2%)	9
Cardiac disorders
Aortic valve disease	1/38 (2.6%)	1	0/33 (0%)	0
Sinus tachycardia	1/38 (2.6%)	1	0/33 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/38 (0%)	0	1/33 (3%)	1
Diarrhea	1/38 (2.6%)	1	1/33 (3%)	1
Enterocolitis	0/38 (0%)	0	1/33 (3%)	1
Lower gastrointestinal hemorrhage	0/38 (0%)	0	1/33 (3%)	1
Nausea	1/38 (2.6%)	1	0/33 (0%)	0
Toothache	0/38 (0%)	0	1/33 (3%)	1
Vomiting	1/38 (2.6%)	1	0/33 (0%)	0
General disorders
Fatigue	7/38 (18.4%)	7	5/33 (15.2%)	7
Immune system disorders
Allergic reaction	1/38 (2.6%)	1	1/33 (3%)	1
Infections and infestations
Lung infection	0/38 (0%)	0	1/33 (3%)	1
Soft tissue infection	1/38 (2.6%)	1	0/33 (0%)	0
Urinary tract infection	1/38 (2.6%)	1	1/33 (3%)	1
Investigations
Alanine aminotransferase increased	2/38 (5.3%)	2	2/33 (6.1%)	2
Aspartate aminotransferase increased	3/38 (7.9%)	3	3/33 (9.1%)	3
Cholesterol high	0/38 (0%)	0	3/33 (9.1%)	3
Creatinine increased	5/38 (13.2%)	5	6/33 (18.2%)	9
INR increased	0/38 (0%)	0	1/33 (3%)	1
Lipase increased	1/38 (2.6%)	1	0/33 (0%)	0
Lymphocyte count decreased	0/38 (0%)	0	1/33 (3%)	1
Neutrophil count decreased	1/38 (2.6%)	1	0/33 (0%)	0
Platelet count decreased	4/38 (10.5%)	4	4/33 (12.1%)	4
Weight loss	1/38 (2.6%)	1	0/33 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/38 (2.6%)	1	0/33 (0%)	0
Dehydration	2/38 (5.3%)	2	0/33 (0%)	0
Hyperglycemia	5/38 (13.2%)	6	4/33 (12.1%)	7
Hypertriglyceridemia	3/38 (7.9%)	3	4/33 (12.1%)	7
Hypokalemia	0/38 (0%)	0	1/33 (3%)	1
Hyponatremia	0/38 (0%)	0	2/33 (6.1%)	2
Nervous system disorders
Depressed level of consciousness	0/38 (0%)	0	1/33 (3%)	1
Seizure	0/38 (0%)	0	1/33 (3%)	1
Syncope	2/38 (5.3%)	2	0/33 (0%)	0
Renal and urinary disorders
Proteinuria	0/38 (0%)	0	2/33 (6.1%)	2
Renal hemorrhage	0/38 (0%)	0	1/33 (3%)	1
Urinary tract obstruction	0/38 (0%)	0	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/38 (5.3%)	2	0/33 (0%)	0
Pleuritic pain	0/38 (0%)	0	1/33 (3%)	1
Pneumonitis	2/38 (5.3%)	2	1/33 (3%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	1/38 (2.6%)	1	2/33 (6.1%)	2
Vascular disorders
Hypertension	2/38 (5.3%)	2	3/33 (9.1%)	3
Hypotension	1/38 (2.6%)	1	2/33 (6.1%)	2
Other (Not Including Serious) Adverse Events
	Arm I (Everolimus)		Arm II (Everolimus With Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/38 (84.2%)		32/33 (97%)
Blood and lymphatic system disorders
Anemia	22/38 (57.9%)	163	21/33 (63.6%)	116
Cardiac disorders
Atrial flutter	1/38 (2.6%)	1	0/33 (0%)	0
Sinus bradycardia	0/38 (0%)	0	1/33 (3%)	1
Gastrointestinal disorders
Abdominal pain	0/38 (0%)	0	1/33 (3%)	1
Colitis	0/38 (0%)	0	1/33 (3%)	1
Constipation	1/38 (2.6%)	1	1/33 (3%)	1
Diarrhea	8/38 (21.1%)	27	15/33 (45.5%)	41
Mucositis oral	11/38 (28.9%)	16	7/33 (21.2%)	7
Nausea	0/38 (0%)	0	2/33 (6.1%)	2
Toothache	0/38 (0%)	0	1/33 (3%)	1
Vomiting	3/38 (7.9%)	3	4/33 (12.1%)	6
General disorders
Edema limbs	0/38 (0%)	0	2/33 (6.1%)	2
Fatigue	20/38 (52.6%)	116	23/33 (69.7%)	92
Pain	0/38 (0%)	0	1/33 (3%)	1
Immune system disorders
Allergic reaction	3/38 (7.9%)	4	5/33 (15.2%)	7
Infections and infestations
Abdominal infection	0/38 (0%)	0	1/33 (3%)	1
Tooth infection	0/38 (0%)	0	1/33 (3%)	1
Wound infection	1/38 (2.6%)	1	1/33 (3%)	1
Injury, poisoning and procedural complications
Wound dehiscence	0/38 (0%)	0	1/33 (3%)	1
Investigations
Alanine aminotransferase increased	6/38 (15.8%)	8	4/33 (12.1%)	7
Alkaline phosphatase increased	1/38 (2.6%)	1	0/33 (0%)	0
Aspartate aminotransferase increased	10/38 (26.3%)	12	7/33 (21.2%)	22
CD4 lymphocytes decreased	0/38 (0%)	0	1/33 (3%)	1
Cholesterol high	17/38 (44.7%)	92	17/33 (51.5%)	63
Creatinine increased	15/38 (39.5%)	75	22/33 (66.7%)	87
Lymphocyte count decreased	0/38 (0%)	0	1/33 (3%)	1
Neutrophil count decreased	6/38 (15.8%)	13	2/33 (6.1%)	2
Platelet count decreased	6/38 (15.8%)	35	13/33 (39.4%)	31
Weight loss	0/38 (0%)	0	2/33 (6.1%)	6
Metabolism and nutrition disorders
Anorexia	2/38 (5.3%)	4	0/33 (0%)	0
Hyperglycemia	21/38 (55.3%)	86	21/33 (63.6%)	90
Hypertriglyceridemia	23/38 (60.5%)	100	24/33 (72.7%)	90
Hypoalbuminemia	1/38 (2.6%)	1	0/33 (0%)	0
Hypokalemia	0/38 (0%)	0	1/33 (3%)	1
Hyponatremia	0/38 (0%)	0	1/33 (3%)	1
Hypophosphatemia	1/38 (2.6%)	1	0/33 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/38 (2.6%)	1	0/33 (0%)	0
Generalized muscle weakness	1/38 (2.6%)	1	0/33 (0%)	0
Myalgia	0/38 (0%)	0	1/33 (3%)	1
Pain in extremity	0/38 (0%)	0	1/33 (3%)	1
Nervous system disorders
Dizziness	1/38 (2.6%)	2	0/33 (0%)	0
Headache	1/38 (2.6%)	2	0/33 (0%)	0
Peripheral motor neuropathy	0/38 (0%)	0	1/33 (3%)	1
Psychiatric disorders
Psychiatric disorders - Other, specify	0/38 (0%)	0	1/33 (3%)	2
Renal and urinary disorders
Proteinuria	0/38 (0%)	0	4/33 (12.1%)	13
Urinary retention	0/38 (0%)	0	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/38 (0%)	0	1/33 (3%)	2
Dyspnea	2/38 (5.3%)	2	0/33 (0%)	0
Epistaxis	0/38 (0%)	0	1/33 (3%)	3
Hypoxia	1/38 (2.6%)	1	0/33 (0%)	0
Laryngeal mucositis	1/38 (2.6%)	1	0/33 (0%)	0
Pleural effusion	1/38 (2.6%)	1	0/33 (0%)	0
Pneumonitis	2/38 (5.3%)	2	6/33 (18.2%)	15
Skin and subcutaneous tissue disorders
Dry skin	1/38 (2.6%)	1	0/33 (0%)	0
Erythema multiforme	12/38 (31.6%)	34	9/33 (27.3%)	19
Pruritus	2/38 (5.3%)	2	0/33 (0%)	0
Rash maculo-papular	0/38 (0%)	0	1/33 (3%)	3
Vascular disorders
Hypertension	10/38 (26.3%)	74	12/33 (36.4%)	60
Thromboembolic event	1/38 (2.6%)	2	1/33 (3%)	1
Vascular disorders - Other, specify	0/38 (0%)	0	1/33 (3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.