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Sorafenib Tosylate and Bevacizumab in Treating Patients With Advanced Kidney Cancer

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ClinicalTrials.gov Identifier: NCT00126503
Recruitment Status : Completed
First Posted : August 4, 2005
Results First Posted : June 28, 2013
Last Update Posted : January 15, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chromophobe Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Papillary Renal Cell Carcinoma
Recurrent Renal Cell Carcinoma
Sarcomatoid Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Interventions Biological: Bevacizumab
Drug: Sorafenib Tosylate
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
Enrollment 73
Recruitment Details This Phase I/II study was open 5/2005 through 12/2010.
Pre-assignment Details 73 patients consented, 4 of whom were determined to be ineligible.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description Sorafenib will be taken orally twice daily beginning on day 1 and continued for 28 days which will be defined as a cycle. Bevacizumab will be administered once every 14 days (with up to a 3 day window before or after 14 days to allow for unforeseen scheduling problems) beginning on day 1. Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1.
Period Title: Overall Study
Started 48 21
Completed 1 0
Not Completed 47 21
Reason Not Completed
disease progression             23             14
Withdrawal by Subject             0             1
alternative therapy             1             1
other complicating disease             4             1
Death             3             0
Adverse Event             13             3
non-compliant             1             0
Physician Decision             2             1
Arm/Group Title Phase I Phase II Total
Hide Arm/Group Description Sorafenib will be taken orally twice daily beginning on day 1 and continued for 28 days which will be defined as a cycle. Bevacizumab will be administered once every 14 days (with up to a 3 day window before or after 14 days to allow for unforeseen scheduling problems) beginning on day 1. Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1. Total of all reporting groups
Overall Number of Baseline Participants 48 21 69
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 21 participants 69 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  72.9%
19
  90.5%
54
  78.3%
>=65 years
13
  27.1%
2
   9.5%
15
  21.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 21 participants 69 participants
65  (1) 58  (1) 62  (1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 21 participants 69 participants
Female
8
  16.7%
7
  33.3%
15
  21.7%
Male
40
  83.3%
14
  66.7%
54
  78.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 48 participants 21 participants 69 participants
48 21 69
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of BAY 43-9006 (Sorafenib)in Combination With Bevacizumab (Phase I)
Hide Description The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) < 500/mm3 for > 7 days, ANC < 1000/mm3 with fever > 101 degrees Fahrenheit, platelet count < 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) >= Grade 3.
Time Frame at 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled to determine the safety of BAY 43-9006 (Sorafenib) in combination with Bevacizumab
Arm/Group Title Phase I
Hide Arm/Group Description:
Sorafenib will be taken orally twice daily beginning on day 1 and continued for 28 days which will be defined as a cycle. Bevacizumab will be administered once every 14 days (with up to a 3-day window before or after 14 days to allow for unforeseen scheduling problems) beginning on day 1.
Overall Number of Participants Analyzed 48
Measure Type: Number
Unit of Measure: mg
200
2.Primary Outcome
Title Maximum Tolerated Dose of Bevacizumab in Combination With BAY 43-9006 (Sorafenib)(Phase I)
Hide Description The highest dose in milligrams (mg) of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) < 500/mm3 for > 7 days, ANC < 1000/mm3 with fever > 101 degrees Fahrenheit, platelet count < 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) >= Grade 3.
Time Frame at 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled to determine the safety of BAY 43-9006 (Sorafenib) in combination with Bevacizumab
Arm/Group Title Phase I
Hide Arm/Group Description:
Sorafenib will be taken orally twice daily beginning on day 1 and continued for 28 days which will be defined as a cycle. Bevacizumab will be administered once every 14 days (with up to a 3 day window before or after 14 days to allow for unforeseen scheduling problems) beginning on day 1.
Overall Number of Participants Analyzed 48
Measure Type: Number
Unit of Measure: mg/kg
5
3.Primary Outcome
Title Objective Response
Hide Description Objective response as determined by RECIST v. 1.0 (measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions)or last date known alive
Time Frame Every 8 weeks to date of progression
Hide Outcome Measure Data
Hide Analysis Population Description
Patients available for measurement of response to treatment with regimen. 7 Phase I and 4 Phase II patients were not available for measurement of response, respectively: disease progression (5, 2), complicating disease (1, 0), death on-study (1, 0), toxicity (0, 1), and alternative treatment (0, 1). All were counted as clinical progression.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description:
The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. The highest dose in milligrams/kilograms of body weight mg/kg of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability. No Phase I patients moved to the Phase II cohort.
Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1. No Phase II patients were in the Phase I cohort.
Overall Number of Participants Analyzed 41 17
Measure Type: Number
Unit of Measure: participants
Complete Response 0 0
Partial Response 23 3
Progressive Disease 2 0
Stable Disease 16 14
4.Secondary Outcome
Title Overall Survival
Hide Description Months from date on-study to expired or last date known alive
Time Frame on-study to date of expired or last date known alive
Hide Outcome Measure Data
Hide Analysis Population Description
All treated patients available for determination of overall survival. No patients in the Phase I cohort moved to the Phase II cohort. No Phase II patients were in the Phase I cohort.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description:
The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. The highest dose in milligrams/kilograms of body weight mg/kg of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability.
Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1.
Overall Number of Participants Analyzed 48 21
Median (Full Range)
Unit of Measure: months
24
(1 to 73)
25
(5 to 59)
5.Secondary Outcome
Title Progression-free Survival
Hide Description Duration of months of progression-free survival (PFS). Determined by months to progressive disease or to last date known alive without progressive disease.
Time Frame on-study to date of progression or last date known alive without progression
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who underwent treatment. No patients in the Phase I cohort moved to the Phase II cohort. No Phase II patients were in the Phase I cohort.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description:
The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. The highest dose in milligrams/kilograms of body weight mg/kg of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability.
Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1.
Overall Number of Participants Analyzed 48 21
Median (Full Range)
Unit of Measure: months
11
(1 to 56)
15
(1 to 49)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I Phase II
Hide Arm/Group Description Sorafenib will be taken orally twice daily beginning on day 1 and continued for 28 days which will be defined as a cycle. Bevacizumab will be administered once every 14 days (with up to a 3 day window before or after 14 days to allow for unforeseen scheduling problems) beginning on day 1. Sorafenib will be taken orally once daily at 200 mg beginning on day -14 and continued for 28 days per cycle. There is no planned interruption. Bevacizumab 5mg/kg IV will be administered every 14 days (+/- 3 days) beginning on day 1.
All-Cause Mortality
Phase I Phase II
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase I Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/48 (35.42%)      8/21 (38.10%)    
Cardiac disorders     
Cardiac ischemia/infarction  3/48 (6.25%)  3 1/21 (4.76%)  1
Supraventricular and nodal arrhythmia-atrial fibrillation  1/48 (2.08%)  2 0/21 (0.00%)  0
Cardiac General-other  1/48 (2.08%)  1 0/21 (0.00%)  0
Supraventricular and nodal arrhythmia-atrial flutter  1/48 (2.08%)  1 0/21 (0.00%)  0
Gastrointestinal disorders     
Pain-abdomen NOS  3/48 (6.25%)  3 1/21 (4.76%)  1
Obstruction, GI-gallbladder  0/48 (0.00%)  0 1/21 (4.76%)  1
Nausea  0/48 (0.00%)  0 1/21 (4.76%)  1
Vomiting  0/48 (0.00%)  0 1/21 (4.76%)  1
Perforation, GI-colon  0/48 (0.00%)  0 1/21 (4.76%)  1
stricture/stenosis (including anastomotic), GI-jejunum  1/48 (2.08%)  1 0/21 (0.00%)  0
Diarrhea  1/48 (2.08%)  1 0/21 (0.00%)  0
Oral mucositis  3/48 (6.25%)  3 0/21 (0.00%)  0
General disorders     
Edema-limb  1/48 (2.08%)  1 0/21 (0.00%)  0
Death not associated with CTCAE term-Disease progression NOS  2/48 (4.17%)  2 0/21 (0.00%)  0
Wound complication, non-infectious  0/48 (0.00%)  0 1/21 (4.76%)  1
Fatigue  2/48 (4.17%)  2 0/21 (0.00%)  0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC < 1.0 x 10e9/L)  0/48 (0.00%)  0 1/21 (4.76%)  1
Infections and infestations     
Infection with unknown ANC-pancreas  1/48 (2.08%)  1 0/21 (0.00%)  0
Infection with unknown ANC-lung (pneumonia)  1/48 (2.08%)  1 0/21 (0.00%)  0
Infection-Other  1/48 (2.08%)  1 0/21 (0.00%)  0
Infection with Grade 1 or 2 neutrophils (ANC < 1.0 x 10e9/L)-skin (cellulitis)  2/48 (4.17%)  2 1/21 (4.76%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils-bone (osteomyelitis)  0/48 (0.00%)  0 1/21 (4.76%)  1
Investigations     
weight loss  1/48 (2.08%)  1 0/21 (0.00%)  0
Metabolism and nutrition disorders     
Hypokalemia  1/48 (2.08%)  1 0/21 (0.00%)  0
Hypoglycemia  1/48 (2.08%)  1 0/21 (0.00%)  0
Hypercalcemia  1/48 (2.08%)  1 0/21 (0.00%)  0
Hyperbilirubinemia  0/48 (0.00%)  0 1/21 (4.76%)  1
Dehydration  0/48 (0.00%)  0 1/21 (4.76%)  1
Hyperkalemia  0/48 (0.00%)  0 1/21 (4.76%)  1
Hyponatremia  0/48 (0.00%)  0 1/21 (4.76%)  1
Musculoskeletal and connective tissue disorders     
Pain-chest wall  1/48 (2.08%)  1 0/21 (0.00%)  0
Musculoskeletal/soft tissue-Other  2/48 (4.17%)  2 0/21 (0.00%)  0
Pain-joint  1/48 (2.08%)  1 0/21 (0.00%)  0
Fracture  2/48 (4.17%)  2 0/21 (0.00%)  0
Pain-back  1/48 (2.08%)  1 0/21 (0.00%)  0
Nervous system disorders     
CNS cerebrovascular ischemia  1/48 (2.08%)  1 0/21 (0.00%)  0
Neuropathy - sensory  1/48 (2.08%)  1 0/21 (0.00%)  0
Somnomolence/depressed level of consciousness  1/48 (2.08%)  1 0/21 (0.00%)  0
Renal and urinary disorders     
Proteinuria  1/48 (2.08%)  1 0/21 (0.00%)  0
Hyperuricemia  1/48 (2.08%)  1 0/21 (0.00%)  0
Renal failure  0/48 (0.00%)  0 2/21 (9.52%)  2
Respiratory, thoracic and mediastinal disorders     
Hemorrhage, pulmonary/upper respiratory-nose  1/48 (2.08%)  1 0/21 (0.00%)  0
Dyspnea  1/48 (2.08%)  1 1/21 (4.76%)  1
Skin and subcutaneous tissue disorders     
palmar-plantar paresthesia  10/48 (20.83%)  10 0/21 (0.00%)  0
Vascular disorders     
Vascular-other  1/48 (2.08%)  1 0/21 (0.00%)  0
Thrombosis/thrombus/embolism  1/48 (2.08%)  1 0/21 (0.00%)  0
Hypertension  10/48 (20.83%)  10 1/21 (4.76%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   48/48 (100.00%)      21/21 (100.00%)    
Blood and lymphatic system disorders     
Leukocytes (total WBC)  0/48 (0.00%)  0 1/21 (4.76%)  4
Lymphopenia  0/48 (0.00%)  0 3/21 (14.29%)  4
Cardiac disorders     
Palpitations  0/48 (0.00%)  0 1/21 (4.76%)  1
Left ventricular systolic dysfunction  0/48 (0.00%)  0 1/21 (4.76%)  1
Supraventricular and nodal arrhythmia-atrial tachycardia/paroxysmal atrial tachycardia  0/48 (0.00%)  0 1/21 (4.76%)  2
Ear and labyrinth disorders     
Otitis, middle ear (non-infectious)  0/48 (0.00%)  0 1/21 (4.76%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils-external ear  0/48 (0.00%)  0 1/21 (4.76%)  1
Endocrine disorders     
Thyroid function, low (hypothyroidism)  0/48 (0.00%)  0 3/21 (14.29%)  3
Endocrine other  0/48 (0.00%)  0 1/21 (4.76%)  1
Eye disorders     
Dry eye syndrome  4/48 (8.33%)  8 0/21 (0.00%)  0
Ocular/visual-Other  0/48 (0.00%)  0 2/21 (9.52%)  2
Vision-blurred vision  8/48 (16.67%)  9 1/21 (4.76%)  1
Vision-flashing lights/floaters  0/48 (0.00%)  0 3/21 (14.29%)  3
Watery eye (epiphora, tearing)  3/48 (6.25%)  4 0/21 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils-Eye NOS  0/48 (0.00%)  0 1/21 (4.76%)  1
Occular surface disease  0/48 (0.00%)  0 1/21 (4.76%)  1
Gastrointestinal disorders     
Anorexia *  28/48 (58.33%)  72 10/21 (47.62%)  11
Colitis *  0/48 (0.00%)  0 1/21 (4.76%)  1
constipation *  22/48 (45.83%)  38 8/21 (38.10%)  12
Dental-teeth  0/48 (0.00%)  0 2/21 (9.52%)  4
Diarrhea  33/48 (68.75%)  171 9/21 (42.86%)  29
Distension/bloating, abdominal  4/48 (8.33%)  10 0/21 (0.00%)  0
Dry mouth/salivary gland (xerostomia)  5/48 (10.42%)  8 4/21 (19.05%)  4
Dysphagia  7/48 (14.58%)  12 3/21 (14.29%)  4
Esophagitis  0/48 (0.00%)  0 1/21 (4.76%)  1
fistula-GI anus  0/48 (0.00%)  0 1/21 (4.76%)  1
Flatulence  18/48 (37.50%)  32 4/21 (19.05%)  5
Gastrointestinal-Other  8/48 (16.67%)  14 1/21 (4.76%)  1
Heartburn, dyspepsia  21/48 (43.75%)  41 6/21 (28.57%)  9
Hemorrhage, GI-lower GI NOS  0/48 (0.00%)  0 1/21 (4.76%)  1
Hemorrhage, GI oral cavity  4/48 (8.33%)  6 4/21 (19.05%)  4
Hemorrhage, GI rectum  4/48 (8.33%)  4 2/21 (9.52%)  2
Hemorrhoids  9/48 (18.75%)  11 1/21 (4.76%)  1
Mucositis/stomatitis-anus/rectum (functional/symptomatic)  3/48 (6.25%)  13 1/21 (4.76%)  1
Mucositis/stomatitis-oral cavity (clinical exam)  23/48 (47.92%)  43 9/21 (42.86%)  10
Nausea  25/48 (52.08%)  57 9/21 (42.86%)  23
Pain-stomach  6/48 (12.50%)  10 0/21 (0.00%)  0
Vomiting  16/48 (33.33%)  28 5/21 (23.81%)  9
Chelitis  0/48 (0.00%)  0 1/21 (4.76%)  1
Infection with unknown ANC-stomach  0/48 (0.00%)  0 1/21 (4.76%)  1
Leak (including anastomatic)-GI-rectum  0/48 (0.00%)  0 1/21 (4.76%)  1
General disorders     
Constitutional symptoms Other *  3/48 (6.25%)  5 1/21 (4.76%)  1
Edema head and neck  3/48 (6.25%)  4 1/21 (4.76%)  1
Edema limb  7/48 (14.58%)  13 6/21 (28.57%)  6
Fatigue  38/48 (79.17%)  140 13/21 (61.90%)  37
Fever (in the absence of neutropenia, with neutropenia defined as ANC < 1.0 x 10e9/L  3/48 (6.25%)  3 2/21 (9.52%)  3
Flu-like syndrome  3/48 (6.25%)  6 2/21 (9.52%)  2
Pain-abdomen NOS  17/48 (35.42%)  35 6/21 (28.57%)  11
Pain-anus/rectum  4/48 (8.33%)  5 0/21 (0.00%)  0
Pain-back  17/48 (35.42%)  30 8/21 (38.10%)  17
Pain-bone  4/48 (8.33%)  7 1/21 (4.76%)  2
Pain-chest/thorax  6/48 (12.50%)  6 4/21 (19.05%)  7
Pain-dental/periodontal  4/48 (8.33%)  9 0/21 (0.00%)  0
Pain-oral cavity/gums  8/48 (16.67%)  12 1/21 (4.76%)  1
Pain-Other/NOS  10/48 (20.83%)  14 4/21 (19.05%)  8
Pain-pelvis  0/48 (0.00%)  0 1/21 (4.76%)  2
Pain-sinus  4/48 (8.33%)  9 3/21 (14.29%)  3
Rigor, chills  9/48 (18.75%)  13 6/21 (28.57%)  7
Pain-neck  6/48 (12.50%)  6 3/21 (14.29%)  3
Tumor pain  3/48 (6.25%)  8 0/21 (0.00%)  0
Pain-chest wall  3/48 (6.25%)  3 0/21 (0.00%)  0
Immune system disorders     
allergic reaction/hypersensivity *  0/48 (0.00%)  0 1/21 (4.76%)  1
allergic rhinitis *  18/48 (37.50%)  33 10/21 (47.62%)  10
Infections and infestations     
Hemoglobin  9/48 (18.75%)  30 3/21 (14.29%)  9
Infection-Other  0/48 (0.00%)  0 2/21 (9.52%)  3
Infection with normal ANC or Grade 1 or 2 neutrophils-cellulitis  3/48 (6.25%)  3 0/21 (0.00%)  0
Infection with unknown ANC-cellulitis  0/48 (0.00%)  0 1/21 (4.76%)  1
Infection with unknown ANC-soft tissue  0/48 (0.00%)  0 2/21 (9.52%)  2
Infection with unknown ANC-wound  0/48 (0.00%)  0 1/21 (4.76%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils-sinus  0/48 (0.00%)  0 2/21 (9.52%)  2
Mucositis/stomatitis (functional/symptomatic)-Oral cavity  0/48 (0.00%)  0 7/21 (33.33%)  10
Injury, poisoning and procedural complications     
Burn  0/48 (0.00%)  0 2/21 (9.52%)  2
Investigations     
ALT/SGPT (serum glutamine pyruvic transminase)   11/48 (22.92%)  28 4/21 (19.05%)  9
AST, SGOT (serum glutamine oxaloacetic transminase)   11/48 (22.92%)  30 4/21 (19.05%)  9
Hypercalcemia  0/48 (0.00%)  0 1/21 (4.76%)  1
Platelets  4/48 (8.33%)  18 1/21 (4.76%)  5
Weight loss  26/48 (54.17%)  67 9/21 (42.86%)  19
Alkaline phosphatase  4/48 (8.33%)  6 1/21 (4.76%)  1
Bicarbonate, serum-low  0/48 (0.00%)  0 2/21 (9.52%)  6
Hyperbilirubinemia  3/48 (6.25%)  3 1/21 (4.76%)  2
Hypophosphatemia  11/48 (22.92%)  54 5/21 (23.81%)  9
Partial prothrombin time (PTT)  0/48 (0.00%)  0 1/21 (4.76%)  1
Triglyceride, serum-high  0/48 (0.00%)  0 1/21 (4.76%)  2
Metabolism and nutrition disorders     
Creatinine  9/48 (18.75%)  24 2/21 (9.52%)  5
Dehydration  3/48 (6.25%)  4 0/21 (0.00%)  0
Hypercholesterolemia  0/48 (0.00%)  0 1/21 (4.76%)  3
Hyperglycemia  11/48 (22.92%)  26 4/21 (19.05%)  40
Hyperkalemia  5/48 (10.42%)  9 1/21 (4.76%)  2
Hypocalcemia  5/48 (10.42%)  8 1/21 (4.76%)  1
Hypoglycemia  3/48 (6.25%)  8 2/21 (9.52%)  5
Hypokalemia  5/48 (10.42%)  8 4/21 (19.05%)  9
Hyponatremia  11/48 (22.92%)  22 3/21 (14.29%)  24
Metabolic/laboratory-Other  0/48 (0.00%)  0 2/21 (9.52%)  2
Obesity  4/48 (8.33%)  8 3/21 (14.29%)  4
Hypoalbuminemia  0/48 (0.00%)  0 4/21 (19.05%)  15
Weight gain  4/48 (8.33%)  5 0/21 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Extemity-lower (gait/walking)  0/48 (0.00%)  0 1/21 (4.76%)  1
Muscle weakness, generalized or specific area-upper extremity/whole body/generalized  3/48 (6.25%)  3 1/21 (4.76%)  1
Musculoskeletal/soft tissue-Other  5/48 (10.42%)  7 0/21 (0.00%)  0
Pain-joint  17/48 (35.42%)  35 6/21 (28.57%)  16
Arthritis (non-septic)  0/48 (0.00%)  0 1/21 (4.76%)  1
Pain-extremity. limb  16/48 (33.33%)  31 8/21 (38.10%)  20
Pain-buttock  0/48 (0.00%)  0 1/21 (4.76%)  1
Pain-muscle  10/48 (20.83%)  11 3/21 (14.29%)  3
Myositis  0/48 (0.00%)  0 1/21 (4.76%)  1
Nervous system disorders     
Dizziness  11/48 (22.92%)  19 5/21 (23.81%)  5
Memory impairment  5/48 (10.42%)  6 1/21 (4.76%)  1
Neurology-Other  0/48 (0.00%)  0 1/21 (4.76%)  2
Neuropathy - sensory  15/48 (31.25%)  42 5/21 (23.81%)  7
Pain-Head/headache  26/48 (54.17%)  53 13/21 (61.90%)  20
Syncope/fainting  0/48 (0.00%)  0 1/21 (4.76%)  1
Taste alteration (dysgeusia)  14/48 (29.17%)  26 5/21 (23.81%)  6
Extrapyramidal/involuntary movement/restlessnes  0/48 (0.00%)  0 1/21 (4.76%)  1
Seizure  0/48 (0.00%)  0 1/21 (4.76%)  1
Psychiatric disorders     
Insomnia  11/48 (22.92%)  13 6/21 (28.57%)  6
Mood alteration-agitation  0/48 (0.00%)  0 1/21 (4.76%)  1
Mood alteration-anxiety  10/48 (20.83%)  12 2/21 (9.52%)  2
Mood alteration-depression  10/48 (20.83%)  11 2/21 (9.52%)  2
Confusion  3/48 (6.25%)  3 0/21 (0.00%)  0
Renal and urinary disorders     
Hemorrhage, GU urinary  0/48 (0.00%)  0 4/21 (19.05%)  4
Proteinuria  11/48 (22.92%)  49 9/21 (42.86%)  56
Renal/Genitourinary-Other  0/48 (0.00%)  0 2/21 (9.52%)  2
Uric acid, serum-high (hyperuricemia)  0/48 (0.00%)  0 3/21 (14.29%)  3
Urinary frequency/urgency  5/48 (10.42%)  7 2/21 (9.52%)  4
Hemoglobinuria  0/48 (0.00%)  0 2/21 (9.52%)  3
Reproductive system and breast disorders     
Hemorrhage, GU vaginal  0/48 (0.00%)  0 1/21 (4.76%)  3
Pain-breast  3/48 (6.25%)  4 0/21 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchospasm-wheezing *  0/48 (0.00%)  0 1/21 (4.76%)  1
Cough *  19/48 (39.58%)  30 10/21 (47.62%)  13
Dyspnea  10/48 (20.83%)  16 4/21 (19.05%)  6
Hemorrhage, pulmonary/upper respiratory-nose  15/48 (31.25%)  26 9/21 (42.86%)  13
Pain-throat, pharynx  10/48 (20.83%)  17 5/21 (23.81%)  11
Pulmonary\upper respiratory-Other  8/48 (16.67%)  13 4/21 (19.05%)  6
Voice changes/dysarthria  33/48 (68.75%)  58 14/21 (66.67%)  21
Hiccoughs  0/48 (0.00%)  0 1/21 (4.76%)  2
Infection with normal ANC or Grade 1 or 2 neutrophils-lung (pneumonia)  0/48 (0.00%)  0 1/21 (4.76%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils-upper airway NOS  0/48 (0.00%)  0 2/21 (9.52%)  2
pneumonitis/pumonary infiltrates  0/48 (0.00%)  0 1/21 (4.76%)  1
Skin and subcutaneous tissue disorders     
Bruising (in absence of Grade 3/4 thromboctyopenia) *  4/48 (8.33%)  4 2/21 (9.52%)  2
Dermatology/Skin-Other  14/48 (29.17%)  31 6/21 (28.57%)  16
Dry skin  16/48 (33.33%)  26 7/21 (33.33%)  8
hair loss-scalp or body  5/48 (10.42%)  15 6/21 (28.57%)  6
Nail changes  5/48 (10.42%)  6 1/21 (4.76%)  1
Pruritis  10/48 (20.83%)  15 5/21 (23.81%)  7
Rash/desquamation  18/48 (37.50%)  30 9/21 (42.86%)  15
Rash acne/actiform  13/48 (27.08%)  17 3/21 (14.29%)  3
palmar/plantar paresthesia  27/48 (56.25%)  195 17/21 (80.95%)  41
Sweating/diphoresis  5/48 (10.42%)  10 3/21 (14.29%)  4
Hyperpigmentation  0/48 (0.00%)  0 1/21 (4.76%)  1
Pain-skin  0/48 (0.00%)  0 1/21 (4.76%)  1
Pain-scalp  10/48 (20.83%)  12 1/21 (4.76%)  1
Telangiectasia  0/48 (0.00%)  0 1/21 (4.76%)  1
Vascular disorders     
Flushing  4/48 (8.33%)  5 1/21 (4.76%)  1
Hypertension  20/48 (41.67%)  54 15/21 (71.43%)  26
Vascular-other  0/48 (0.00%)  0 1/21 (4.76%)  1
Hypotension  3/48 (6.25%)  3 0/21 (0.00%)  0
Vessel injury-vein-extremity-limb  0/48 (0.00%)  0 1/21 (4.76%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
To depict results of this Phases I/II study accurately, each phase was entered as an ARM to enable separation of the data by phase. Events reported in the Adverse Event and Serious Adverse Event sections include AEs and SAEs from Phase I and Phase II
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jeffrey Sosman, MD
Organization: Vanderbilt-Ingram Cancer Center
Phone: 615-936-3048
EMail: jeff.sosman@vanderbilt.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00126503     History of Changes
Other Study ID Numbers: NCI-2009-00066
NCI-2009-00066 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000434814
URO 470 ( Other Identifier: Vanderbilt-Ingram Cancer Center )
6555 ( Other Identifier: CTEP )
U01CA099177 ( U.S. NIH Grant/Contract )
P30CA068485 ( U.S. NIH Grant/Contract )
First Submitted: August 2, 2005
First Posted: August 4, 2005
Results First Submitted: November 16, 2012
Results First Posted: June 28, 2013
Last Update Posted: January 15, 2015