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Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00378703
Collaborator
(none)
361
Enrollment
559
Locations
4
Arms
114.2
Actual Duration (Months)
0.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

Condition or Disease Intervention/Treatment Phase
  • Biological: Bevacizumab
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Drug: Sorafenib Tosylate
  • Drug: Temsirolimus
 Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess progression-free survival on each arm of combination targeted therapy (CTT) compared to that of bevacizumab alone.
SECONDARY OBJECTIVES:

  1. To assess the significance of changes in tumor size over early time points as a predictor of progression-free survival (PFS).

  2. To quantify the number and percent of patients who have stable disease at 6 months of therapy (failure to progress) in each treatment arm of CTT in patients with metastatic renal cell carcinoma (RCC).

  3. To evaluate the safety of each treatment arm of combination targeted therapy (CTT) in patients with metastatic RCC.

  4. To assess overall survival in each arm of the study. V. To assess the objective response rate in each treatment arm of CTT in patients with metastatic RCC.

  5. To assess pathology, angiogenesis histology and to assess activation status of mitogen activated protein (MAP) kinase and vascular endothelial growth factor receptor 2 (VEGFR2) pathways and relate to clinical outcome.

TERTIARY OBJECTIVES:

  1. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib (sorafenib tosylate) including angiogenesis, monooxygenases polymorphisms and multi-drug resistance (MDR).

  2. To relate changes in tumor perfusion and vascular permeability on serial dynamic contrast-enhanced magnetic resonance imaging (MRI) to clinical outcome and radiologic regression detected by other standard methods.

  3. To assess the potential of dynamic contrast-enhanced (DCE)-MRI imaging as a biomarker for response to therapy and/or as a prognostic indicator of disease progression.

  4. To assess site readiness and ability in acquiring DCE-MRI data. V. To determine the relationship between tumor and blood biomarkers and clinical outcomes of patients treated with the combination of targeted agents.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM A: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

ARM B: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.

ARM C: Patients receive bevacizumab as in Arm A and sorafenib tosylate orally (PO) twice daily (BID) on days 1-5, 8-12, 15-19, and 22-26.

ARM D: Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.

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

After completion of study treatment, patients are followed up periodically for 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
361 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The BeST Trial: A Randomized Phase II Study of VEGF, RAF Kinase, and mTOR Combination Targeted Therapy (CTT) With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma
Actual Study Start Date :
Sep 14, 2007
Actual Primary Completion Date :
Feb 7, 2014
Actual Study Completion Date :
Mar 21, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A (bevacizumab)

Patients receive 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

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies
    Experimental: Arm B (bevacizumab and temsirolimus)

    Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.

    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

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Drug: Temsirolimus
    Given IV
    Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel

    		•
    Experimental: Arm C (bevacizumab and sorafenib tosylate)

    Patients receive bevacizumab as in Arm A and sorafenib tosylate PO BID on days 1-5, 8-12, 15-19, and 22-26.

    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

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Drug: Sorafenib Tosylate
    Given PO
    Other Names:
  • BAY 43-9006 Tosylate
  • BAY 54-9085
  • Nexavar
  • sorafenib

    		•
    Experimental: Arm D (sorafenib tosylate and temsirolimus)

    Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.

    Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Drug: Sorafenib Tosylate
    Given PO
    Other Names:
  • BAY 43-9006 Tosylate
  • BAY 54-9085
  • Nexavar
  • sorafenib

    • Drug: Temsirolimus
    Given IV
    Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years]

      Progression-free survival is defined as time from randomization to clinical evidence of disease progression or death from any cause without progression. Patients alive without progression were censored at the date of last disease assessment.

    Secondary Outcome Measures

    1. Proportion of Patients With Stable Disease at 6 Months [Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years]

      Patients whose date of progression was after 6 months or who were disease-free at last follow-up beyond 6 months were considered to be stable at 6 months and all other patients were not.

    2. Overall Survival [Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years]

      Overall survival was defined as the time from randomization to death. Patients alive at last contact were censored on the date of last contact.

    3. Objective Response Rate [Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years]

      Response was assessed using Solid Tumor Response Criteria (RECIST). Patients with complete responses or partial responses are considered having an objective response.

    Eligibility Criteria

    Criteria

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

    • Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion

    • Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry

    • Previous nephrectomy is required with the following exceptions:

    • Primary tumor =< 5 cm, or

    • Extensive liver (> 30% of liver parenchymal) or multiple (> 5) bone metastases, making nephrectomy a clinically questionable procedure

    • Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava

    • No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted

    • No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease

    • No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment

    • Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization

    • No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks

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

    • Life expectancy of greater than 12 weeks

    • Hemoglobin (Hgb) >= 9.0 g/dL (transfusions allowed prior to enrollment)

    • White blood count (WBC) >= 3,000/mm^3

    • Absolute granulocyte count (AGC) >= 1,200/mm^3

    • Platelet count >= 100,000/mm^3

    • Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 55 ml/min

    • Total bilirubin =< 1.5 x ULN

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (or =< 5.0 x ULN in the presence of liver metastases)

    • International normalized ratio (INR) =< 1.5

    • Activated partial thromboplastin time (aPTT) within normal limits

    • Fasting cholesterol < 350 mg/dL (9.0 mmol/L)

    • Fasting triglycerides < 400 mg/dL (4.56 mmol/L)

    • Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of randomization

    • No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab

    • No history of bleeding diathesis or coagulopathy

    • Any condition that impairs patient's ability to swallow pills will make patient ineligible

    • No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization

    • No anticipated need for major surgery during the course of the study

    • No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =< 1.5)

    • No clinically significant cardiovascular disease, defined as one of the following:

    • Patients with uncontrolled hypertension (blood pressure > 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =< 150/100 mm/Hg on stable antihypertensive regimen are eligible

    • Myocardial infarction or unstable angina < 24 weeks prior to registration

    • New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris

    • Grade II or greater peripheral vascular disease

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

    • No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is > 0.5, 24-hour urine protein is to be obtained and the level must be < 1000 mg for patient enrollment

    • NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

    • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements

    • Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible:

    • Phenytoin

    • Carbamazepine

    • Phenobarbital

    • Rifampin

    • Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity

    • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study

    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 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    4 The University of Arizona Medical Center-University Campus Tucson Arizona United States 85724
    5 Mercy Hospital Fort Smith Fort Smith Arkansas United States 72903
    6 NEA Baptist Memorial Hospital Jonesboro Arkansas United States 72401
    7 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    8 Alta Bates Summit Medical Center-Herrick Campus Berkeley California United States 94704
    9 Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California United States 91505
    10 Mills-Peninsula Medical Center Burlingame California United States 94010
    11 East Bay Radiation Oncology Center Castro Valley California United States 94546
    12 Eden Hospital Medical Center Castro Valley California United States 94546
    13 Valley Medical Oncology Consultants-Castro Valley Castro Valley California United States 94546
    14 Bay Area Breast Surgeons Inc Emeryville California United States 94608
    15 Valley Medical Oncology Consultants-Fremont Fremont California United States 94538
    16 Glendale Memorial Hospital and Health Center Glendale California United States 91204
    17 Marin Cancer Care Inc Greenbrae California United States 94904
    18 Marin General Hospital Greenbrae California United States 94904
    19 UC San Diego Moores Cancer Center La Jolla California United States 92093
    20 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    21 Contra Costa Regional Medical Center Martinez California United States 94553-3156
    22 Fremont - Rideout Cancer Center Marysville California United States 95901
    23 El Camino Hospital Mountain View California United States 94040
    24 Palo Alto Medical Foundation-Camino Division Mountain View California United States 94040
    25 Sutter Cancer Research Consortium Novato California United States 94945
    26 Highland General Hospital Oakland California United States 94602
    27 Alta Bates Summit Medical Center - Summit Campus Oakland California United States 94609
    28 Bay Area Tumor Institute Oakland California United States 94609
    29 Hematology and Oncology Associates-Oakland Oakland California United States 94609
    30 Tom K Lee Inc Oakland California United States 94609
    31 Saint Joseph Hospital - Orange Orange California United States 92868
    32 Palo Alto Medical Foundation Health Care Palo Alto California United States 94301
    33 Valley Care Health System - Pleasanton Pleasanton California United States 94588
    34 Valley Medical Oncology Consultants Pleasanton California United States 94588
    35 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    36 University of California San Diego San Diego California United States 92103
    37 Veterans Administration-San Diego Medical Center San Diego California United States 92161
    38 California Pacific Medical Center-Pacific Campus San Francisco California United States 94115
    39 Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo California United States 94806
    40 Gene Upshaw Memorial Tahoe Forest Cancer Center Truckee California United States 96161
    41 Sutter Solano Medical Center/Cancer Center Vallejo California United States 94589
    42 The Medical Center of Aurora Aurora Colorado United States 80012
    43 University of Colorado Hospital Aurora Colorado United States 80045
    44 Boulder Community Hospital Boulder Colorado United States 80301
    45 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    46 UCHealth Memorial Hospital Central Colorado Springs Colorado United States 80909
    47 Porter Adventist Hospital Denver Colorado United States 80210
    48 University of Colorado Denver Colorado United States 80217-3364
    49 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    50 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    51 Rose Medical Center Denver Colorado United States 80220
    52 Colorado Cancer Research Program NCORP Denver Colorado United States 80222
    53 The Shaw Regional Cancer Center Edwards Colorado United States 81632
    54 Swedish Medical Center Englewood Colorado United States 80113
    55 Poudre Valley Hospital Fort Collins Colorado United States 80524
    56 Valley View Hospital Cancer Center Glenwood Springs Colorado United States 81601
    57 Saint Mary's Hospital and Regional Medical Center Grand Junction Colorado United States 81501
    58 North Colorado Medical Center Greeley Colorado United States 80631
    59 Saint Anthony Hospital Lakewood Colorado United States 80228
    60 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    61 Longmont United Hospital Longmont Colorado United States 80501
    62 McKee Medical Center Loveland Colorado United States 80539
    63 Montrose Memorial Hospital Montrose Colorado United States 81401
    64 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    65 North Suburban Medical Center Thornton Colorado United States 80229
    66 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    67 Hartford Hospital Hartford Connecticut United States 06102
    68 Beebe Medical Center Lewes Delaware United States 19958
    69 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    70 Boca Raton Regional Hospital Boca Raton Florida United States 33486
    71 Mayo Clinic in Florida Jacksonville Florida United States 32224-9980
    72 UF Cancer Center at Orlando Health Orlando Florida United States 32806
    73 John B Amos Cancer Center Columbus Georgia United States 31904
    74 Northeast Georgia Medical Center-Gainesville Gainesville Georgia United States 30501
    75 Medical Center of Central Georgia Macon Georgia United States 31201
    76 Kootenai Cancer Center Post Falls Idaho United States 83854
    77 Saint Anthony's Health Alton Illinois United States 62002
    78 Rush - Copley Medical Center Aurora Illinois United States 60504
    79 MacNeal Hospital and Cancer Center Berwyn Illinois United States 60402
    80 Saint Joseph Medical Center Bloomington Illinois United States 61701
    81 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    82 Graham Hospital Association Canton Illinois United States 61520
    83 Illinois CancerCare-Canton Canton Illinois United States 61520
    84 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    85 Memorial Hospital Carthage Illinois United States 62321
    86 Hematology and Oncology Associates Chicago Illinois United States 60611
    87 Northwestern University Chicago Illinois United States 60611
    88 Jesse Brown Veterans Affairs Medical Center Chicago Illinois United States 60612
    89 University of Illinois Chicago Illinois United States 60612
    90 Presence Resurrection Medical Center Chicago Illinois United States 60631
    91 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    92 Decatur Memorial Hospital Decatur Illinois United States 62526
    93 Heartland Cancer Research NCORP Decatur Illinois United States 62526
    94 Advocate Sherman Hospital Elgin Illinois United States 60123
    95 AMITA Health Alexian Brothers Medical Center Elk Grove Village Illinois United States 60007
    96 Eureka Hospital Eureka Illinois United States 61530
    97 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    98 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    99 Galesburg Cottage Hospital Galesburg Illinois United States 61401
    100 Illinois CancerCare-Cottage Galesburg Illinois United States 61401
    101 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    102 Ingalls Memorial Hospital Harvey Illinois United States 60426
    103 Illinois CancerCare-Havana Havana Illinois United States 62644
    104 Mason District Hospital Havana Illinois United States 62644
    105 Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois United States 60035
    106 Hopedale Medical Complex - Hospital Hopedale Illinois United States 61747
    107 Midwest Center for Hematology Oncology Joliet Illinois United States 60432
    108 Joliet Oncology-Hematology Associates Limited Joliet Illinois United States 60435
    109 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    110 Kewanee Hospital Kewanee Illinois United States 61443
    111 AMITA Health Adventist Medical Center La Grange Illinois United States 60525
    112 NorthShore Hematology Oncology-Libertyville Libertyville Illinois United States 60048
    113 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    114 Mcdonough District Hospital Macomb Illinois United States 61455
    115 Garneau, Stewart C MD (UIA Investigator) Moline Illinois United States 61265
    116 Porubcin, Michael MD (UIA Investigator) Moline Illinois United States 61265
    117 Sharis, Christine M MD (UIA Investigator) Moline Illinois United States 61265
    118 Spector, David MD (UIA Investigator) Moline Illinois United States 61265
    119 Stoffel, Thomas J MD (UIA Investigator) Moline Illinois United States 61265
    120 Trinity Medical Center Moline Illinois United States 61265
    121 Holy Family Medical Center Monmouth Illinois United States 61462
    122 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    123 Good Samaritan Regional Health Center Mount Vernon Illinois United States 62864
    124 AMG Oncology - Naperville Naperville Illinois United States 60540
    125 DuPage Medical Group-Ogden Naperville Illinois United States 60563
    126 Illinois Cancer Specialists-Niles Niles Illinois United States 60714
    127 Bromenn Regional Medical Center Normal Illinois United States 61761
    128 Community Cancer Center Foundation Normal Illinois United States 61761
    129 Illinois CancerCare-Community Cancer Center Normal Illinois United States 61761
    130 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    131 Ottawa Regional Hospital and Healthcare Center Ottawa Illinois United States 61350
    132 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    133 OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois United States 61554
    134 Pekin Hospital Pekin Illinois United States 61554
    135 Proctor Hospital Peoria Illinois United States 61614
    136 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    137 Methodist Medical Center of Illinois Peoria Illinois United States 61636
    138 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    139 Illinois CancerCare-Peru Peru Illinois United States 61354
    140 Illinois Valley Hospital Peru Illinois United States 61354
    141 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    142 Perry Memorial Hospital Princeton Illinois United States 61356
    143 Swedish American Hospital Rockford Illinois United States 61104
    144 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    145 Hematology Oncology Associates of Illinois - Skokie Skokie Illinois United States 60076
    146 Illinois CancerCare-Spring Valley Spring Valley Illinois United States 61362
    147 Saint Margaret's Hospital Spring Valley Illinois United States 61362
    148 Memorial Medical Center Springfield Illinois United States 62781
    149 Carle Cancer Center Urbana Illinois United States 61801
    150 Franciscan Saint Francis Health-Beech Grove Beech Grove Indiana United States 46107
    151 Elkhart Clinic Elkhart Indiana United States 46514-2098
    152 Michiana Hematology Oncology PC-Elkhart Elkhart Indiana United States 46514
    153 Elkhart General Hospital Elkhart Indiana United States 46515
    154 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    155 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    156 Richard L. Roudebush Veterans Affairs Medical Center Indianapolis Indiana United States 46202
    157 Sidney and Lois Eskenazi Hospital Indianapolis Indiana United States 46202
    158 Community Howard Regional Health Kokomo Indiana United States 46904
    159 IU Health La Porte Hospital La Porte Indiana United States 46350
    160 Horizon Oncology Research LLC Lafayette Indiana United States 47905
    161 Franciscan Saint Anthony Health-Michigan City Michigan City Indiana United States 46360
    162 Michiana Hematology Oncology PC-Mishawaka Mishawaka Indiana United States 46545
    163 Saint Joseph Regional Medical Center-Mishawaka Mishawaka Indiana United States 46545
    164 Michiana Hematology Oncology PC-Plymouth Plymouth Indiana United States 46563
    165 Reid Health Richmond Indiana United States 47374
    166 Memorial Hospital of South Bend South Bend Indiana United States 46601
    167 Michiana Hematology Oncology PC-South Bend South Bend Indiana United States 46601
    168 South Bend Clinic South Bend Indiana United States 46617
    169 Northern Indiana Cancer Research Consortium South Bend Indiana United States 46628
    170 Michiana Hematology Oncology PC-Westville Westville Indiana United States 46391
    171 McFarland Clinic PC - Ames Ames Iowa United States 50010
    172 Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa United States 52722
    173 University of Iowa Healthcare Cancer Services Quad Cities Bettendorf Iowa United States 52722
    174 Mercy Hospital Cedar Rapids Iowa United States 52403
    175 Oncology Associates at Mercy Medical Center Cedar Rapids Iowa United States 52403
    176 Genesis Medical Center - East Campus Davenport Iowa United States 52803
    177 Genesis Medical Center - West Campus Davenport Iowa United States 52804
    178 Mercy Capitol Des Moines Iowa United States 50307
    179 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    180 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    181 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    182 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    183 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    184 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    185 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    186 Mercy Medical Center - North Iowa Mason City Iowa United States 50401
    187 Ottumwa Regional Health Center Ottumwa Iowa United States 52501
    188 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    189 Mercy Medical Center-Sioux City Sioux City Iowa United States 51104
    190 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    191 Hospital District Sixth of Harper County Anthony Kansas United States 67003
    192 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    193 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    194 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    195 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    196 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    197 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    198 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    199 Southwest Medical Center Liberal Kansas United States 67901
    200 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    201 Menorah Medical Center Overland Park Kansas United States 66209
    202 Radiation Oncology Practice Corporation Southwest Overland Park Kansas United States 66210
    203 Saint Luke's South Hospital Overland Park Kansas United States 66213
    204 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    205 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    206 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    207 Shawnee Mission Medical Center-KCCC Shawnee Mission Kansas United States 66204
    208 Cotton O'Neil Cancer Center / Stormont Vail Health Topeka Kansas United States 66606
    209 Saint Francis Hospital and Medical Center - Topeka Topeka Kansas United States 66606
    210 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    211 Associates In Womens Health Wichita Kansas United States 67208
    212 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    213 Cancer Center of Kansas - Wichita Wichita Kansas United States 67214
    214 Via Christi Regional Medical Center Wichita Kansas United States 67214
    215 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    216 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    217 Doctors Carrol, Sheth, Raghavan Louisville Kentucky United States 40215
    218 Baton Rouge General Medical Center Baton Rouge Louisiana United States 70806
    219 Mary Bird Perkins Cancer Center Baton Rouge Louisiana United States 70809
    220 Ochsner Health Center-Summa Baton Rouge Louisiana United States 70809
    221 Louisiana State University Health Science Center New Orleans Louisiana United States 70112
    222 University Medical Center New Orleans New Orleans Louisiana United States 70112
    223 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    224 Eastern Maine Medical Center Bangor Maine United States 04401
    225 Saint Mary's Regional Medical Center Lewiston Maine United States 04240
    226 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    227 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    228 Union Hospital of Cecil County Elkton Maryland United States 21921
    229 Frederick Memorial Hospital Frederick Maryland United States 21701
    230 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    231 Bixby Medical Center Adrian Michigan United States 49221
    232 Hickman Cancer Center Adrian Michigan United States 49221
    233 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    234 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    235 Bronson Battle Creek Battle Creek Michigan United States 49017
    236 Spectrum Health Big Rapids Hospital Big Rapids Michigan United States 49307
    237 Beaumont Hospital-Dearborn Dearborn Michigan United States 48124
    238 Ascension Saint John Hospital Detroit Michigan United States 48236
    239 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    240 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    241 Hurley Medical Center Flint Michigan United States 48503
    242 Genesys Regional Medical Center-West Flint Campus Flint Michigan United States 48532
    243 Cancer Research Consortium of West Michigan NCORP Grand Rapids Michigan United States 49503
    244 Mercy Health Saint Mary's Grand Rapids Michigan United States 49503
    245 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    246 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    247 Allegiance Health Jackson Michigan United States 49201
    248 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    249 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    250 Borgess Medical Center Kalamazoo Michigan United States 49048
    251 Sparrow Hospital Lansing Michigan United States 48912
    252 Saint Mary Mercy Hospital Livonia Michigan United States 48154
    253 Mercy Memorial Hospital Monroe Michigan United States 48162
    254 Toledo Clinic Cancer Centers-Monroe Monroe Michigan United States 48162
    255 Mercy Health Partners-Hackley Campus Muskegon Michigan United States 49442
    256 Mercy Health Mercy Campus Muskegon Michigan United States 49444
    257 Lakeland Hospital Niles Niles Michigan United States 49120
    258 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    259 Lake Huron Medical Center Port Huron Michigan United States 48060
    260 Saint Mary's of Michigan Saginaw Michigan United States 48601
    261 Lakeland Medical Center Saint Joseph Saint Joseph Michigan United States 49085
    262 Marie Yeager Cancer Center Saint Joseph Michigan United States 49085
    263 Oncology Care Associates PLLC Saint Joseph Michigan United States 49085
    264 Providence Hospital-Southfield Cancer Center Southfield Michigan United States 48075
    265 Munson Medical Center Traverse City Michigan United States 49684
    266 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    267 Metro Health Hospital Wyoming Michigan United States 49519
    268 Medini, Eitan MD (UIA Investigator) Alexandria Minnesota United States 56308
    269 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    270 Mercy Hospital Coon Rapids Minnesota United States 55433
    271 Essentia Health Cancer Center Duluth Minnesota United States 55805
    272 Essentia Health Saint Mary's Medical Center Duluth Minnesota United States 55805
    273 Miller-Dwan Hospital Duluth Minnesota United States 55805
    274 Fairview-Southdale Hospital Edina Minnesota United States 55435
    275 Etzell, Paul S MD (UIA Investigator) Fergus Falls Minnesota United States 56537
    276 Swenson, Wade II, MD (UIA Investigator) Fergus Falls Minnesota United States 56537
    277 Unity Hospital Fridley Minnesota United States 55432
    278 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    279 Meeker County Memorial Hospital Litchfield Minnesota United States 55355
    280 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    281 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    282 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    283 Virginia Piper Cancer Institute Minneapolis Minnesota United States 55407
    284 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    285 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    286 Mayo Clinic Rochester Minnesota United States 55905
    287 Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    288 Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    289 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    290 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    291 Regions Hospital Saint Paul Minnesota United States 55101
    292 Saint Joseph's Hospital - Healtheast Saint Paul Minnesota United States 55102
    293 United Hospital Saint Paul Minnesota United States 55102
    294 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    295 Ridgeview Medical Center Waconia Minnesota United States 55387
    296 Rice Memorial Hospital Willmar Minnesota United States 56201
    297 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    298 Woodwinds Health Campus Woodbury Minnesota United States 55125
    299 University of Mississippi Medical Center Jackson Mississippi United States 39216
    300 Singing River Hospital Pascagoula Mississippi United States 39581
    301 Southeast Missouri Hospital Cape Girardeau Missouri United States 63701
    302 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    303 Centerpoint Medical Center LLC Independence Missouri United States 64057
    304 Mercy Hospital Joplin Joplin Missouri United States 64804
    305 Truman Medical Center Kansas City Missouri United States 64108
    306 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    307 Radiation Oncology Practice Corporation South Kansas City Missouri United States 64114
    308 Saint Joseph Health Center Kansas City Missouri United States 64114
    309 North Kansas City Hospital Kansas City Missouri United States 64116
    310 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri United States 64118
    311 Research Medical Center Kansas City Missouri United States 64132
    312 Radiation Oncology Practice Corporation - North Kansas City Missouri United States 64154
    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 Heartland Regional Medical Center Saint Joseph Missouri United States 64507
    316 Saint Joseph Oncology Inc Saint Joseph Missouri United States 64507
    317 Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri United States 63109
    318 Saint Louis University Hospital Saint Louis Missouri United States 63110
    319 Washington University School of Medicine Saint Louis Missouri United States 63110
    320 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    321 Center for Cancer Care and Research Saint Louis Missouri United States 63141
    322 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    323 Saint Louis-Cape Girardeau CCOP Saint Louis Missouri United States 63141
    324 Mercy Hospital Springfield Springfield Missouri United States 65804
    325 CoxHealth South Hospital Springfield Missouri United States 65807
    326 Billings Clinic Cancer Center Billings Montana United States 59101
    327 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    328 Saint Vincent Healthcare Billings Montana United States 59101
    329 Montana Cancer Consortium NCORP Billings Montana United States 59102
    330 Saint Vincent Frontier Cancer Center Billings Montana United States 59102
    331 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    332 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    333 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    334 Berdeaux, Donald MD (UIA Investigator) 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 Community Medical Hospital Missoula Montana United States 59804
    345 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    346 CHI Health Saint Francis Grand Island Nebraska United States 68803
    347 CHI Health Good Samaritan Kearney Nebraska United States 68847
    348 Great Plains Health Callahan Cancer Center North Platte Nebraska United States 69101
    349 University of Nebraska Medical Center Omaha Nebraska United States 68198
    350 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    351 Nevada Cancer Research Foundation CCOP Las Vegas Nevada United States 89106
    352 Portsmouth Regional Hospital Portsmouth New Hampshire United States 03802
    353 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    354 Veterans Adminstration New Jersey Health Care System East Orange New Jersey United States 07018-1095
    355 Morristown Medical Center Morristown New Jersey United States 07960
    356 Virtua Memorial Mount Holly New Jersey United States 08060
    357 Rutgers New Jersey Medical School Newark New Jersey United States 07101
    358 Overlook Hospital Summit New Jersey United States 07902
    359 Inspira Medical Center Vineland Vineland New Jersey United States 08360
    360 Virtua Voorhees Voorhees New Jersey United States 08043
    361 Montefiore Medical Center-Wakefield Campus Bronx New York United States 10466
    362 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    363 Kings County Hospital Brooklyn New York United States 11203
    364 State University of New York Downstate Medical Center Brooklyn New York United States 11203
    365 Roswell Park Cancer Institute Buffalo New York United States 14263
    366 Mary Imogene Bassett Hospital Cooperstown New York United States 13326
    367 Hematology Oncology Associates of Central New York-East Syracuse East Syracuse New York United States 13057
    368 Glens Falls Hospital Glens Falls New York United States 12801
    369 Northwell Health NCORP Lake Success New York United States 11042
    370 North Shore University Hospital Manhasset New York United States 11030
    371 Orange Regional Medical Center Middletown New York United States 10940
    372 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    373 Columbia University/Herbert Irving Cancer Center New York New York United States 10032
    374 University of Rochester Rochester New York United States 14642
    375 Mission Hospital Inc-Memorial Campus Asheville North Carolina United States 28801
    376 Cone Health Cancer Center at Alamance Regional Burlington North Carolina United States 27215
    377 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
    378 Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina United States 27534
    379 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    380 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    381 Vidant Oncology-Kinston Kinston North Carolina United States 28501
    382 FirstHealth of the Carolinas-Moore Regional Hospital Pinehurst North Carolina United States 28374
    383 Rutherford Hospital Rutherfordton North Carolina United States 28139
    384 Southeast Clinical Oncology Research (SCOR) Consortium NCORP Winston-Salem North Carolina United States 27104
    385 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    386 Mid Dakota Clinic Bismarck North Dakota United States 58501
    387 Saint Alexius Medical Center Bismarck North Dakota United States 58501
    388 Sanford Bismarck Medical Center Bismarck North Dakota United States 58501
    389 Cleveland Clinic Akron General Akron Ohio United States 44307
    390 Mary Rutan Hospital Bellefontaine Ohio United States 43311
    391 Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio United States 43402
    392 Mercy Medical Center Canton Ohio United States 44708
    393 Aultman Health Foundation Canton Ohio United States 44710
    394 Adena Regional Medical Center Chillicothe Ohio United States 45601
    395 The Christ Hospital Cincinnati Ohio United States 45219
    396 MetroHealth Medical Center Cleveland Ohio United States 44109
    397 North Coast Cancer Care-Clyde Clyde Ohio United States 43410
    398 Riverside Methodist Hospital Columbus Ohio United States 43214
    399 Columbus NCI Community Oncology Research Program Columbus Ohio United States 43215
    400 Grant Medical Center Columbus Ohio United States 43215
    401 Mount Carmel Health Center West Columbus Ohio United States 43222
    402 Doctors Hospital Columbus Ohio United States 43228
    403 Grandview Hospital Dayton Ohio United States 45405
    404 Good Samaritan Hospital - Dayton Dayton Ohio United States 45406
    405 Miami Valley Hospital Dayton Ohio United States 45409
    406 Samaritan North Health Center Dayton Ohio United States 45415
    407 Dayton NCI Community Oncology Research Program Dayton Ohio United States 45420
    408 Veteran Affairs Medical Center Dayton Ohio United States 45428
    409 Grady Memorial Hospital Delaware Ohio United States 43015
    410 Hematology Oncology Center Incorporated Elyria Ohio United States 44035
    411 Mercy Cancer Center-Elyria Elyria Ohio United States 44035
    412 Blanchard Valley Hospital Findlay Ohio United States 45840
    413 Atrium Medical Center-Middletown Regional Hospital Franklin Ohio United States 45005-1066
    414 Fremont Memorial Hospital Fremont Ohio United States 43420
    415 Wayne Hospital Greenville Ohio United States 45331
    416 Kettering Medical Center Kettering Ohio United States 45429
    417 Fairfield Medical Center Lancaster Ohio United States 43130
    418 Saint Rita's Medical Center Lima Ohio United States 45801
    419 Lima Memorial Hospital Lima Ohio United States 45804
    420 Marietta Memorial Hospital Marietta Ohio United States 45750
    421 Saint Luke's Hospital Maumee Ohio United States 43537
    422 Toledo Clinic Cancer Centers-Maumee Maumee Ohio United States 43537
    423 Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee Ohio United States 43537
    424 Knox Community Hospital Mount Vernon Ohio United States 43050
    425 Licking Memorial Hospital Newark Ohio United States 43055
    426 Fisher-Titus Medical Center Norwalk Ohio United States 44857
    427 Saint Charles Hospital Oregon Ohio United States 43616
    428 Toledo Clinic Cancer Centers-Oregon Oregon Ohio United States 43616
    429 Firelands Regional Medical Center Sandusky Ohio United States 44870
    430 North Coast Cancer Care Sandusky Ohio United States 44870
    431 Springfield Regional Medical Center Springfield Ohio United States 45505
    432 ProMedica Flower Hospital Sylvania Ohio United States 43560
    433 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    434 The Toledo Hospital/Toledo Children's Hospital Toledo Ohio United States 43606
    435 Saint Vincent Mercy Medical Center Toledo Ohio United States 43608
    436 University of Toledo Toledo Ohio United States 43614
    437 Toledo Community Hospital Oncology Program CCOP Toledo Ohio United States 43617
    438 Mercy Saint Anne Hospital Toledo Ohio United States 43623
    439 Toledo Clinic Cancer Centers-Toledo Toledo Ohio United States 43623
    440 Upper Valley Medical Center Troy Ohio United States 45373
    441 Fulton County Health Center Wauseon Ohio United States 43567
    442 Saint Ann's Hospital Westerville Ohio United States 43081
    443 Clinton Memorial Hospital Wilmington Ohio United States 45177
    444 Greene Memorial Hospital Xenia Ohio United States 45385
    445 Genesis Healthcare System Cancer Care Center Zanesville Ohio United States 43701
    446 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    447 Natalie Warren Bryant Cancer Center at Saint Francis Tulsa Oklahoma United States 74136
    448 Bay Area Hospital Coos Bay Oregon United States 97420
    449 Kaiser Permanente Northwest Portland Oregon United States 97227
    450 Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania United States 18103
    451 Saint Luke's University Hospital-Bethlehem Campus Bethlehem Pennsylvania United States 18015
    452 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    453 Geisinger Medical Center Danville Pennsylvania United States 17822
    454 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    455 Lancaster General Hospital Lancaster Pennsylvania United States 17604
    456 Central PA Hematology-Medical Oncology Associates PC Lemoyne Pennsylvania United States 17043
    457 Riddle Memorial Hospital Media Pennsylvania United States 19063
    458 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    459 University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    460 Pennsylvania Hospital Philadelphia Pennsylvania United States 19107
    461 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    462 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    463 Einstein Medical Center Philadelphia Philadelphia Pennsylvania United States 19141
    464 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    465 Mercy Hospital Scranton Pennsylvania United States 18501
    466 Hematology and Oncology Associates of North East Pennsylvania Scranton Pennsylvania United States 18508
    467 Scranton Hematology Oncology Scranton Pennsylvania United States 18510
    468 Geisinger Medical Group State College Pennsylvania United States 16801
    469 Reading Hospital West Reading Pennsylvania United States 19611
    470 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    471 Geisinger South Wilkes-Barre Wilkes-Barre Pennsylvania United States 18765
    472 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    473 Memorial Hospital of Rhode Island Pawtucket Rhode Island United States 02860
    474 AnMed Health Hospital Anderson South Carolina United States 29621
    475 Spartanburg Medical Center Spartanburg South Carolina United States 29303
    476 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    477 Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota United States 57104
    478 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    479 Avera McKennan Hospital and University Health Center Sioux Falls South Dakota United States 57105
    480 Medical X-Ray Center Sioux Falls South Dakota United States 57105
    481 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    482 Vanderbilt-Ingram Cancer Center Cool Springs Franklin Tennessee United States 37067
    483 Jackson-Madison County General Hospital Jackson Tennessee United States 38301
    484 Tennessee Cancer Specialists-Dowell Springs Knoxville Tennessee United States 37909
    485 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    486 East Tennessee Baptist Hospital-Mercy Health Partners Knoxville Tennessee United States 37920
    487 University of Tennessee - Knoxville Knoxville Tennessee United States 37920
    488 University of Tennessee Health Science Center Memphis Tennessee United States 38163
    489 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    490 The Don and Sybil Harrington Cancer Center Amarillo Texas United States 79106
    491 Texas Oncology-Austin Midtown Austin Texas United States 78705
    492 Texas Oncology - Central Austin Cancer Center Austin Texas United States 78731
    493 Texas Oncology - South Austin Cancer Center Austin Texas United States 78745
    494 Texas Oncology-Austin North Austin Texas United States 78758
    495 Texas Oncology Seton Northwest Austin Texas United States 78759
    496 The Center for Cancer and Blood Disorders-Burleson Burleson Texas United States 76115
    497 Texas Oncology-Cedar Park Cedar Park Texas United States 78613
    498 The Center for Cancer and Blood Disorders-Cleburne Cleburne Texas United States 76033
    499 The Center for Cancer and Blood Disorders-Fort Worth Fort Worth Texas United States 76104
    500 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    501 Baylor Saint Luke's Medical Center Houston Texas United States 77030
    502 Ben Taub General Hospital Houston Texas United States 77030
    503 Michael E DeBakey VA Medical Center Houston Texas United States 77030
    504 The Methodist Hospital System Houston Texas United States 77030
    505 The Center for Cancer and Blood Disorders-Mineral Wells Mineral Wells Texas United States 76067
    506 Texas Oncology-Seton Williamson Round Rock Texas United States 78665
    507 Texas Oncology - Round Rock Cancer Center Round Rock Texas United States 78681
    508 Texas Oncology- San Marcos San Marcos Texas United States 78666
    509 The Center for Cancer and Blood Disorders-Weatherford Weatherford Texas United States 76086
    510 Danville Regional Medical Center Danville Virginia United States 24541
    511 Fredericksburg Oncology Inc Fredericksburg Virginia United States 22401
    512 Sovah Health Martinsville Martinsville Virginia United States 24115
    513 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    514 PeaceHealth Saint Joseph Medical Center Bellingham Washington United States 98225
    515 Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington United States 98310
    516 Kadlec Clinic Hematology and Oncology Kennewick Washington United States 99336
    517 Skagit Valley Hospital Mount Vernon Washington United States 98274
    518 Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington United States 98370
    519 Minor and James Medical PLLC Seattle Washington United States 98104
    520 Kaiser Permanente Washington Seattle Washington United States 98112
    521 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    522 University of Washington Medical Center Seattle Washington United States 98195
    523 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    524 Evergreen Hematology and Oncology PS Spokane Washington United States 99218
    525 Rockwood Clinic Spokane Washington United States 99220
    526 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98801
    527 West Virginia University Charleston Division Charleston West Virginia United States 25304
    528 Fox Valley Hematology and Oncology SC-Appleton Appleton Wisconsin United States 54913
    529 Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin United States 54729
    530 HSHS Sacred Heart Hospital Eau Claire Wisconsin United States 54701
    531 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    532 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    533 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    534 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    535 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    536 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    537 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    538 UW Health Oncology-One South Park Madison Wisconsin United States 53715
    539 Dean Hematology and Oncology Clinic Madison Wisconsin United States 53717
    540 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    541 Holy Family Memorial Hospital Manitowoc Wisconsin United States 54221
    542 Bay Area Medical Center Marinette Wisconsin United States 54143
    543 Marshfield Clinic Marshfield Wisconsin United States 54449
    544 Marshfield Medical Center Marshfield Wisconsin United States 54449
    545 Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    546 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    547 Green Bay Oncology - Oconto Falls Oconto Falls Wisconsin United States 54154
    548 Ascension Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    549 Marshfield Clinic-Rice Lake Center Rice Lake Wisconsin United States 54868
    550 Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    551 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    552 Marshfield Clinic-Wausau Center Wausau Wisconsin United States 54401
    553 Diagnostic and Treatment Center Weston Wisconsin United States 54476
    554 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476
    555 Aspirus UW Cancer Center Wisconsin Rapids Wisconsin United States 54494
    556 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    557 Rocky Mountain Oncology Casper Wyoming United States 82609
    558 Welch Cancer Center Sheridan Wyoming United States 82801
    559 Instituto Nacional de Enfermedades Neoplasicas Lima Peru Lima 34

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Keith Flaherty, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00378703
    Other Study ID Numbers:
    • NCI-2009-00533
    • NCI-2009-00533
    • ECOG-E2804
    • CDR0000499788
    • E2804
    • E2804
    • U10CA180820
    • U10CA021115
    First Posted:
    Sep 21, 2006
    Last Update Posted:
    Nov 14, 2018
    Last Verified:
    Oct 1, 2018
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Renal Cell
    Sirolimus
    Bevacizumab
    Antineoplastic Agents, Immunological
    Sorafenib
    Endothelial Growth Factors
    Antibodies
    Immunoglobulins
    Antibodies, Monoclonal
    Immunoglobulin G

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited from ECOG member institutions between September 14, 2007 and December 10, 2010 with a final accrual of 361 patients.
    Pre-assignment Detail
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. bevacizumab: Given IV Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. temsirolimus: Given IV bevacizumab: Given IV Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Sorafenib: Given PO bevacizumab: Given IV Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Sorafenib: Given PO temsirolimus: Given IV
    Period Title: Overall Study
    STARTED 89 91 90 91
    Treated 88 86 90 91
    Eligible and Treated 84 80 83 84
    COMPLETED 0 0 0 0
    NOT COMPLETED 89 91 90 91

    Baseline Characteristics

    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus) Total
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Total of all reporting groups
    Overall Participants 84 80 83 84 331
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    49
    58.3%
    51
    63.8%
    52
    62.7%
    61
    72.6%
    213
    64.4%
    >=65 years
    35
    41.7%
    29
    36.3%
    31
    37.3%
    23
    27.4%
    118
    35.6%
    Sex: Female, Male (Count of Participants)
    Female
    22
    26.2%
    25
    31.3%
    26
    31.3%
    17
    20.2%
    90
    27.2%
    Male
    62
    73.8%
    55
    68.8%
    57
    68.7%
    67
    79.8%
    241
    72.8%
    Region of Enrollment (participants) [Number]
    United States
    84
    100%
    80
    100%
    83
    100%
    84
    100%
    331
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS)
    Description Progression-free survival is defined as time from randomization to clinical evidence of disease progression or death from any cause without progression. Patients alive without progression were censored at the date of last disease assessment.
    Time Frame Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. bevacizumab: Given IV Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. temsirolimus: Given IV bevacizumab: Given IV Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Sorafenib: Given PO bevacizumab: Given IV Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Sorafenib: Given PO temsirolimus: Given IV
    Measure Participants 84 80 83 84
    Median (90% Confidence Interval) [Months]
    7.5
    7.6
    9.2
    7.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm B (Bevacizumab and Temsirolimus)
    Comments Progression-free survival was compared between Arm B (bevacizumab and temsirolimus) and Arm A (bevacizumab alone) using stratified log rank test, stratified on prior cytokine or vaccine therapy and risk category (low/intermediate/high risk)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.89
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm C (Bevacizumab and Sorafenib)
    Comments Progression-free survival was compared between Arm C (bevacizumab and sorafenib) and Arm A (bevacizumab alone) using stratified log rank test, stratified on prior cytokine or vaccine therapy and risk category (low/intermediate/high risk).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.54
    Comments
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm D (Sorafenib and Temsirolimus)
    Comments Progression-free survival was compared between Arm D (sorafenib and temsirolimus) and Arm A (bevacizumab alone) using stratified log rank test, stratified on prior cytokine or vaccine therapy and risk category (low/intermediate/high risk).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.68
    Comments
    Method Log Rank
    Comments
    2. Secondary Outcome
    Title Proportion of Patients With Stable Disease at 6 Months
    Description Patients whose date of progression was after 6 months or who were disease-free at last follow-up beyond 6 months were considered to be stable at 6 months and all other patients were not.
    Time Frame Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. bevacizumab: Given IV Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. temsirolimus: Given IV bevacizumab: Given IV Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Sorafenib: Given PO bevacizumab: Given IV Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Sorafenib: Given PO temsirolimus: Given IV
    Measure Participants 84 80 83 84
    Number (95% Confidence Interval) [Proportion of patients]
    0.548
    0.562
    0.590
    0.524
    3. Secondary Outcome
    Title Overall Survival
    Description Overall survival was defined as the time from randomization to death. Patients alive at last contact were censored on the date of last contact.
    Time Frame Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. bevacizumab: Given IV Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. temsirolimus: Given IV bevacizumab: Given IV Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Sorafenib: Given PO bevacizumab: Given IV Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Sorafenib: Given PO temsirolimus: Given IV
    Measure Participants 84 80 83 84
    Median (90% Confidence Interval) [Months]
    28.6
    24.7
    27.5
    24.3
    4. Secondary Outcome
    Title Objective Response Rate
    Description Response was assessed using Solid Tumor Response Criteria (RECIST). Patients with complete responses or partial responses are considered having an objective response.
    Time Frame Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible, treated patients
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. bevacizumab: Given IV Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. temsirolimus: Given IV bevacizumab: Given IV Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Sorafenib: Given PO bevacizumab: Given IV Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle. Sorafenib: Given PO temsirolimus: Given IV
    Measure Participants 84 80 83 84
    Number (95% Confidence Interval) [Proportion of patients]
    0.133
    0.316
    0.305
    0.202
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm B (Bevacizumab and Temsirolimus)
    Comments The response rate of each combination arm was compared to that of the bevacizumab alone arm.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0076
    Comments Each combination arm was compared with the bevacizumab alone arm. Since there were 3 pairwise comparisons, a Bonferroni--adjusted p-value of 0.017 was considered to be statistically significant.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm C (Bevacizumab and Sorafenib)
    Comments The response rate of each combination arm was compared to that of the bevacizumab alone arm.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0085
    Comments Each combination arm was compared with the bevacizumab alone arm. Since there were 3 pairwise comparisons, a Bonferroni--adjusted p-value of 0.017 was considered to be statistically significant.
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A (Bevacizumab), Arm D (Sorafenib and Temsirolimus)
    Comments The response rate of each combination arm was compared to that of the bevacizumab alone arm.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3006
    Comments Each combination arm was compared with the bevacizumab alone arm. Since there were 3 pairwise comparisons, a Bonferroni--adjusted p-value of 0.017 was considered to be statistically significant.
    Method Fisher Exact
    Comments

    Adverse Events

    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
    Adverse Event Reporting Description
    Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Arm/Group Description Patients receive bevacizumab 10 mg/kg IV over 30-90 minutes on days 1 and 15 in a 28-day cycle. Patients receive temsirolimus 25 mg IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A in a 28-day cycle. Patients receive bevacizumab 5 mg/kg IV over 30-90 minutes on days 1 and 15 and sorafenib 200 mg PO BID on days 1-5, 8-12, 15-19, and 22-26 in a 28-day cycle. Patients receive sorafenib 200 mg PO BID on days 1-28 and temsirolimus as in Arm B in a 28-day cycle.
    All Cause Mortality
    Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 39/88 (44.3%) 66/86 (76.7%) 74/90 (82.2%) 76/91 (83.5%)
    Blood and lymphatic system disorders
    Hemoglobin 0/88 (0%) 2/86 (2.3%) 2/90 (2.2%) 8/91 (8.8%)
    Cardiac disorders
    Atrial fibrillation 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Atrial flutter 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Sinus arrhythmia 1/88 (1.1%) 0/86 (0%) 0/90 (0%) 0/91 (0%)
    Supraventricular tachycardia 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Cardiac-ischemia 1/88 (1.1%) 3/86 (3.5%) 1/90 (1.1%) 1/91 (1.1%)
    Left ventricular diastolic dysfunction 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Left ventricular systolic dysfunction 1/88 (1.1%) 2/86 (2.3%) 1/90 (1.1%) 0/91 (0%)
    Cardiac/heart, pain 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    Eye disorders
    Cataract 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Keratitis 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Gastrointestinal disorders
    Colitis 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Constipation 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Diarrhea w/o prior colostomy 0/88 (0%) 6/86 (7%) 6/90 (6.7%) 9/91 (9.9%)
    Enteritis 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Gastritis 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Ileus 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Muco/stomatitis by exam, oral cavity 0/88 (0%) 1/86 (1.2%) 3/90 (3.3%) 1/91 (1.1%)
    Muco/stomatitis (symptom) oral cavity 0/88 (0%) 2/86 (2.3%) 0/90 (0%) 3/91 (3.3%)
    Nausea 0/88 (0%) 1/86 (1.2%) 2/90 (2.2%) 0/91 (0%)
    Necrosis, colon/cecum/appendix 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Obstruction, colon 1/88 (1.1%) 0/86 (0%) 0/90 (0%) 0/91 (0%)
    Perforation, colon 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Ulcer, anus 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Ulcer, gastric 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 1/91 (1.1%)
    Vomiting 0/88 (0%) 0/86 (0%) 2/90 (2.2%) 0/91 (0%)
    GI-other 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Rectum, hemorrhage 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Abdomen, pain 1/88 (1.1%) 3/86 (3.5%) 6/90 (6.7%) 4/91 (4.4%)
    Anus, pain 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Oral cavity, pain 1/88 (1.1%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Rectum, pain 0/88 (0%) 2/86 (2.3%) 0/90 (0%) 0/91 (0%)
    General disorders
    Fatigue 2/88 (2.3%) 13/86 (15.1%) 10/90 (11.1%) 14/91 (15.4%)
    Fever w/o neutropenia 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Edema limb 0/88 (0%) 3/86 (3.5%) 0/90 (0%) 0/91 (0%)
    Chest/thoracic pain NOS 0/88 (0%) 0/86 (0%) 2/90 (2.2%) 0/91 (0%)
    Immune system disorders
    Allergic reaction 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Infections and infestations
    Infection Gr0-2 neut, abdomen 0/88 (0%) 2/86 (2.3%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, anal/perianl 1/88 (1.1%) 0/86 (0%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, bone 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Infection Gr0-2 neut, dental-tooth 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, kidney 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, lung 0/88 (0%) 3/86 (3.5%) 0/90 (0%) 2/91 (2.2%)
    Infection Gr0-2 neut, rectum 0/88 (0%) 3/86 (3.5%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, salivary 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Infection Gr0-2 neut, sinus 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 1/91 (1.1%)
    Infection Gr0-2 neut, skin 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    Infection Gr0-2 neut, wound 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Infection w/ unk ANC lung 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Infection Gr0-2 neut, blood 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Investigations
    Leukocytes 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 4/91 (4.4%)
    Lymphopenia 0/88 (0%) 3/86 (3.5%) 2/90 (2.2%) 10/91 (11%)
    Neutrophils 0/88 (0%) 3/86 (3.5%) 0/90 (0%) 4/91 (4.4%)
    Platelets 0/88 (0%) 2/86 (2.3%) 1/90 (1.1%) 8/91 (8.8%)
    Cardiac troponin I (cTnI) 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Weight loss 0/88 (0%) 2/86 (2.3%) 3/90 (3.3%) 3/91 (3.3%)
    Alkaline phosphatase 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    ALT, SGPT 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 1/91 (1.1%)
    Amylase 0/88 (0%) 0/86 (0%) 2/90 (2.2%) 4/91 (4.4%)
    AST, SGOT 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Bilirubin 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Hypercholesterolemia 0/88 (0%) 4/86 (4.7%) 0/90 (0%) 5/91 (5.5%)
    Creatinine 0/88 (0%) 1/86 (1.2%) 3/90 (3.3%) 0/91 (0%)
    Lipase 1/88 (1.1%) 2/86 (2.3%) 4/90 (4.4%) 4/91 (4.4%)
    Vital capacity 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Metabolism and nutrition disorders
    Anorexia 2/88 (2.3%) 3/86 (3.5%) 4/90 (4.4%) 3/91 (3.3%)
    Dehydration 0/88 (0%) 5/86 (5.8%) 3/90 (3.3%) 1/91 (1.1%)
    Acidosis 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Hypoalbuminemia 0/88 (0%) 2/86 (2.3%) 0/90 (0%) 0/91 (0%)
    Hypocalcemia 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Hyperglycemia 0/88 (0%) 9/86 (10.5%) 2/90 (2.2%) 16/91 (17.6%)
    Hypoglycemia 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    Hypophosphatemia 2/88 (2.3%) 7/86 (8.1%) 10/90 (11.1%) 30/91 (33%)
    Hyperkalemia 0/88 (0%) 0/86 (0%) 0/90 (0%) 2/91 (2.2%)
    Hypokalemia 0/88 (0%) 2/86 (2.3%) 3/90 (3.3%) 5/91 (5.5%)
    Hyponatremia 0/88 (0%) 3/86 (3.5%) 8/90 (8.9%) 4/91 (4.4%)
    Hypertriglyceridemia 0/88 (0%) 4/86 (4.7%) 0/90 (0%) 5/91 (5.5%)
    Hyperuricemia 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 1/91 (1.1%)
    Musculoskeletal and connective tissue disorders
    Nonneuropathic generalized weakness 0/88 (0%) 0/86 (0%) 2/90 (2.2%) 0/91 (0%)
    Back, pain 1/88 (1.1%) 1/86 (1.2%) 1/90 (1.1%) 3/91 (3.3%)
    Chest wall, pain 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Extremity-limb, pain 0/88 (0%) 1/86 (1.2%) 3/90 (3.3%) 0/91 (0%)
    Joint, pain 2/88 (2.3%) 2/86 (2.3%) 1/90 (1.1%) 2/91 (2.2%)
    Muscle, pain 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 2/91 (2.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Secondary malignancy 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Nervous system disorders
    CNS, hemorrhage 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    CNS cerebrovascular ischemia 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Dizziness 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Memory impairment 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Neuropathy-sensory 0/88 (0%) 1/86 (1.2%) 2/90 (2.2%) 0/91 (0%)
    Seizure 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Syncope 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Head/headache 2/88 (2.3%) 5/86 (5.8%) 4/90 (4.4%) 3/91 (3.3%)
    Neuropathic, pain 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Psychiatric disorders
    Confusion 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Anxiety 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 1/91 (1.1%)
    Depression 0/88 (0%) 0/86 (0%) 2/90 (2.2%) 0/91 (0%)
    Renal and urinary disorders
    Urinary hemorrhage NOS 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Glomerular filtration rate 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 0/91 (0%)
    Proteinuria 9/88 (10.2%) 22/86 (25.6%) 9/90 (10%) 1/91 (1.1%)
    Renal failure 0/88 (0%) 3/86 (3.5%) 2/90 (2.2%) 2/91 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    Lung, hemorrhage 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Nose, hemorrhage 0/88 (0%) 2/86 (2.3%) 0/90 (0%) 0/91 (0%)
    Bronchospasm, wheezing 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Cough 0/88 (0%) 3/86 (3.5%) 0/90 (0%) 2/91 (2.2%)
    Dyspnea 0/88 (0%) 6/86 (7%) 1/90 (1.1%) 2/91 (2.2%)
    Nasal cavity/paranasal sinus reaction 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    Obstruction, airway-bronchus 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 0/91 (0%)
    Pleural effusion (non-malignant) 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 2/91 (2.2%)
    Pneumonitis/pulmonary infiltrates 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 4/91 (4.4%)
    Skin and subcutaneous tissue disorders
    Photosensitivity 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 1/91 (1.1%)
    Pruritus/itching 0/88 (0%) 0/86 (0%) 0/90 (0%) 4/91 (4.4%)
    Rash/desquamation 1/88 (1.1%) 2/86 (2.3%) 3/90 (3.3%) 7/91 (7.7%)
    Rash: acne/acneiform 0/88 (0%) 1/86 (1.2%) 0/90 (0%) 2/91 (2.2%)
    Erythema multiforme 0/88 (0%) 0/86 (0%) 0/90 (0%) 1/91 (1.1%)
    Hand-foot reaction 0/88 (0%) 1/86 (1.2%) 20/90 (22.2%) 3/91 (3.3%)
    Ulceration 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Vascular disorders
    Hypertension 18/88 (20.5%) 15/86 (17.4%) 34/90 (37.8%) 7/91 (7.7%)
    Hypotension 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Thrombosis/thrombus/embolism 2/88 (2.3%) 4/86 (4.7%) 2/90 (2.2%) 2/91 (2.2%)
    Vascular-Other (Specify) 0/88 (0%) 0/86 (0%) 1/90 (1.1%) 0/91 (0%)
    Other (Not Including Serious) Adverse Events
    Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 80/88 (90.9%) 86/86 (100%) 89/90 (98.9%) 90/91 (98.9%)
    Blood and lymphatic system disorders
    Hemoglobin 30/88 (34.1%) 65/86 (75.6%) 37/90 (41.1%) 75/91 (82.4%)
    Eye disorders
    Tearing 0/88 (0%) 5/86 (5.8%) 1/90 (1.1%) 1/91 (1.1%)
    Gastrointestinal disorders
    Constipation 14/88 (15.9%) 24/86 (27.9%) 23/90 (25.6%) 24/91 (26.4%)
    Diarrhea w/o prior colostomy 15/88 (17%) 40/86 (46.5%) 45/90 (50%) 65/91 (71.4%)
    Dry mouth 1/88 (1.1%) 2/86 (2.3%) 2/90 (2.2%) 6/91 (6.6%)
    Flatulence 0/88 (0%) 1/86 (1.2%) 1/90 (1.1%) 7/91 (7.7%)
    Dyspepsia 5/88 (5.7%) 7/86 (8.1%) 19/90 (21.1%) 7/91 (7.7%)
    Muco/stomatitis by exam, oral cavity 2/88 (2.3%) 22/86 (25.6%) 20/90 (22.2%) 13/91 (14.3%)
    Muco/stomatitis (symptom) oral cavity 5/88 (5.7%) 40/86 (46.5%) 33/90 (36.7%) 24/91 (26.4%)
    Nausea 17/88 (19.3%) 37/86 (43%) 38/90 (42.2%) 50/91 (54.9%)
    Vomiting 7/88 (8%) 18/86 (20.9%) 23/90 (25.6%) 24/91 (26.4%)
    Abdomen, pain 4/88 (4.5%) 7/86 (8.1%) 15/90 (16.7%) 24/91 (26.4%)
    Oral cavity, pain 0/88 (0%) 6/86 (7%) 4/90 (4.4%) 4/91 (4.4%)
    General disorders
    Fatigue 48/88 (54.5%) 66/86 (76.7%) 64/90 (71.1%) 75/91 (82.4%)
    Fever w/o neutropenia 2/88 (2.3%) 11/86 (12.8%) 6/90 (6.7%) 13/91 (14.3%)
    Rigors/chills 5/88 (5.7%) 12/86 (14%) 7/90 (7.8%) 8/91 (8.8%)
    Edema head and neck 1/88 (1.1%) 5/86 (5.8%) 0/90 (0%) 6/91 (6.6%)
    Edema limb 5/88 (5.7%) 15/86 (17.4%) 11/90 (12.2%) 18/91 (19.8%)
    Chest/thoracic pain NOS 2/88 (2.3%) 9/86 (10.5%) 3/90 (3.3%) 5/91 (5.5%)
    Immune system disorders
    Allergic reaction 0/88 (0%) 5/86 (5.8%) 0/90 (0%) 4/91 (4.4%)
    Infections and infestations
    Infection Gr0-2 neut, sinus 1/88 (1.1%) 7/86 (8.1%) 3/90 (3.3%) 4/91 (4.4%)
    Investigations
    Leukocytes 4/88 (4.5%) 32/86 (37.2%) 12/90 (13.3%) 46/91 (50.5%)
    Lymphopenia 7/88 (8%) 21/86 (24.4%) 16/90 (17.8%) 28/91 (30.8%)
    Neutrophils 2/88 (2.3%) 21/86 (24.4%) 3/90 (3.3%) 22/91 (24.2%)
    Platelets 13/88 (14.8%) 43/86 (50%) 21/90 (23.3%) 52/91 (57.1%)
    Weight loss 7/88 (8%) 28/86 (32.6%) 31/90 (34.4%) 37/91 (40.7%)
    Alkaline phosphatase 9/88 (10.2%) 19/86 (22.1%) 19/90 (21.1%) 34/91 (37.4%)
    ALT, SGPT 11/88 (12.5%) 23/86 (26.7%) 11/90 (12.2%) 36/91 (39.6%)
    Amylase 5/88 (5.7%) 8/86 (9.3%) 11/90 (12.2%) 9/91 (9.9%)
    AST, SGOT 12/88 (13.6%) 26/86 (30.2%) 23/90 (25.6%) 39/91 (42.9%)
    Bilirubin 3/88 (3.4%) 0/86 (0%) 6/90 (6.7%) 6/91 (6.6%)
    Hypercholesterolemia 11/88 (12.5%) 39/86 (45.3%) 16/90 (17.8%) 34/91 (37.4%)
    Creatinine 25/88 (28.4%) 43/86 (50%) 37/90 (41.1%) 35/91 (38.5%)
    Lipase 7/88 (8%) 13/86 (15.1%) 23/90 (25.6%) 14/91 (15.4%)
    Metabolic/Laboratory-other 2/88 (2.3%) 10/86 (11.6%) 10/90 (11.1%) 8/91 (8.8%)
    Metabolism and nutrition disorders
    Anorexia 12/88 (13.6%) 46/86 (53.5%) 41/90 (45.6%) 48/91 (52.7%)
    Hypoalbuminemia 5/88 (5.7%) 23/86 (26.7%) 17/90 (18.9%) 17/91 (18.7%)
    Bicarbonate 1/88 (1.1%) 5/86 (5.8%) 1/90 (1.1%) 1/91 (1.1%)
    Hypocalcemia 5/88 (5.7%) 16/86 (18.6%) 12/90 (13.3%) 20/91 (22%)
    Hyperglycemia 12/88 (13.6%) 47/86 (54.7%) 30/90 (33.3%) 50/91 (54.9%)
    Hypomagnesemia 1/88 (1.1%) 1/86 (1.2%) 0/90 (0%) 5/91 (5.5%)
    Hypophosphatemia 6/88 (6.8%) 21/86 (24.4%) 29/90 (32.2%) 53/91 (58.2%)
    Hyperkalemia 5/88 (5.7%) 6/86 (7%) 10/90 (11.1%) 5/91 (5.5%)
    Hypokalemia 5/88 (5.7%) 14/86 (16.3%) 7/90 (7.8%) 17/91 (18.7%)
    Hyponatremia 7/88 (8%) 8/86 (9.3%) 19/90 (21.1%) 20/91 (22%)
    Hypertriglyceridemia 17/88 (19.3%) 39/86 (45.3%) 29/90 (32.2%) 42/91 (46.2%)
    Musculoskeletal and connective tissue disorders
    Back, pain 4/88 (4.5%) 11/86 (12.8%) 4/90 (4.4%) 8/91 (8.8%)
    Extremity-limb, pain 2/88 (2.3%) 3/86 (3.5%) 8/90 (8.9%) 7/91 (7.7%)
    Joint, pain 10/88 (11.4%) 18/86 (20.9%) 16/90 (17.8%) 15/91 (16.5%)
    Muscle, pain 2/88 (2.3%) 5/86 (5.8%) 9/90 (10%) 7/91 (7.7%)
    Nervous system disorders
    Taste disturbance 5/88 (5.7%) 29/86 (33.7%) 24/90 (26.7%) 35/91 (38.5%)
    Dizziness 1/88 (1.1%) 3/86 (3.5%) 7/90 (7.8%) 3/91 (3.3%)
    Neuropathy-sensory 2/88 (2.3%) 10/86 (11.6%) 20/90 (22.2%) 11/91 (12.1%)
    Head/headache 13/88 (14.8%) 28/86 (32.6%) 23/90 (25.6%) 22/91 (24.2%)
    Psychiatric disorders
    Insomnia 1/88 (1.1%) 7/86 (8.1%) 7/90 (7.8%) 10/91 (11%)
    Depression 4/88 (4.5%) 13/86 (15.1%) 6/90 (6.7%) 10/91 (11%)
    Renal and urinary disorders
    Glomerular filtration rate 3/88 (3.4%) 5/86 (5.8%) 6/90 (6.7%) 1/91 (1.1%)
    Proteinuria 25/88 (28.4%) 40/86 (46.5%) 45/90 (50%) 2/91 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 9/88 (10.2%) 10/86 (11.6%) 9/90 (10%) 5/91 (5.5%)
    Nose, hemorrhage 18/88 (20.5%) 36/86 (41.9%) 29/90 (32.2%) 22/91 (24.2%)
    Throat/pharynx/larynx, pain 0/88 (0%) 4/86 (4.7%) 5/90 (5.6%) 1/91 (1.1%)
    Cough 7/88 (8%) 22/86 (25.6%) 9/90 (10%) 16/91 (17.6%)
    Dyspnea 8/88 (9.1%) 30/86 (34.9%) 13/90 (14.4%) 21/91 (23.1%)
    Pneumonitis/pulmonary infiltrates 0/88 (0%) 8/86 (9.3%) 0/90 (0%) 4/91 (4.4%)
    Voice changes/dysarthria 9/88 (10.2%) 12/86 (14%) 30/90 (33.3%) 11/91 (12.1%)
    Skin and subcutaneous tissue disorders
    Dry skin 11/88 (12.5%) 21/86 (24.4%) 30/90 (33.3%) 30/91 (33%)
    Alopecia 3/88 (3.4%) 10/86 (11.6%) 13/90 (14.4%) 14/91 (15.4%)
    Nail changes 5/88 (5.7%) 13/86 (15.1%) 13/90 (14.4%) 16/91 (17.6%)
    Pruritus/itching 6/88 (6.8%) 27/86 (31.4%) 9/90 (10%) 29/91 (31.9%)
    Rash/desquamation 3/88 (3.4%) 35/86 (40.7%) 16/90 (17.8%) 41/91 (45.1%)
    Rash: acne/acneiform 3/88 (3.4%) 36/86 (41.9%) 14/90 (15.6%) 39/91 (42.9%)
    Hand-foot reaction 3/88 (3.4%) 15/86 (17.4%) 43/90 (47.8%) 26/91 (28.6%)
    Vascular disorders
    Hypertension 29/88 (33%) 39/86 (45.3%) 42/90 (46.7%) 34/91 (37.4%)
    Hypotension 0/88 (0%) 5/86 (5.8%) 4/90 (4.4%) 1/91 (1.1%)
    Flushing 0/88 (0%) 1/86 (1.2%) 5/90 (5.6%) 4/91 (4.4%)

    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.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG-ACRIN Statistical Office
    Phone 617-632-3012
    Email
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00378703
    Other Study ID Numbers:
    • NCI-2009-00533
    • NCI-2009-00533
    • ECOG-E2804
    • CDR0000499788
    • E2804
    • E2804
    • U10CA180820
    • U10CA021115
    First Posted:
    Sep 21, 2006
    Last Update Posted:
    Nov 14, 2018
    Last Verified:
    Oct 1, 2018