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

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ClinicalTrials.gov Identifier: NCT00378703
Recruitment Status : Completed
First Posted : September 21, 2006
Results First Posted : May 5, 2015
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Carcinoma
Stage IV Renal Cell Cancer AJCC v7
Interventions Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Sorafenib Tosylate
Drug: Temsirolimus
Enrollment 361
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 Details  
Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
Hide 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 [1] 91 [1] 90 [1] 91 [1]
Treated 88 [2] 86 [2] 90 [2] 91 [2]
Eligible and Treated 84 [3] 80 [3] 83 [3] 84 [3]
Completed 0 [4] 0 [4] 0 [4] 0 [4]
Not Completed 89 91 90 91
Reason Not Completed
Disease progression             59             43             48             49
Adverse Event             11             17             20             18
Death             2             2             4             3
Withdrawal by Subject             4             8             5             7
Physician Decision             1             4             1             0
Alternative therapy             4             2             0             0
Other complicated disease             0             2             2             0
Symptomatic deterioration             0             1             0             2
Surgery             1             0             0             1
Joint decision of physician and patient             1             0             0             0
Adverse events and progressive disease             0             0             0             1
Relocation             0             0             1             0
Ineligible             4             7             7             7
Never started treatment             1             4             0             0
Other             1             1             2             3
[1]
Number of patients randomized to this treatment arm.
[2]
Number of patients included in the toxicity analysis.
[3]
Number of patients included in the primary analysis.
[4]
There is no limit to the number of treatment cycles allowed on any treatment arm.
Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus) Total
Hide 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 Number of Baseline Participants 84 80 83 84 331
Hide Baseline Analysis Population Description
Eligible and treated patients are included in this analysis.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 80 participants 83 participants 84 participants 331 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
49
  58.3%
51
  63.7%
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 80 participants 83 participants 84 participants 331 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  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 84 participants 80 participants 83 participants 84 participants 331 participants
84 80 83 84 331
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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

Overall Number of Participants Analyzed 84 80 83 84
Median (90% Confidence Interval)
Unit of Measure: Months
7.5
(5.8 to 10.8)
7.6
(6.7 to 9.2)
9.2
(7.5 to 11.4)
7.4
(5.6 to 7.9)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Patients With Stable Disease at 6 Months
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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

Overall Number of Participants Analyzed 84 80 83 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients
0.548
(0.435 to 0.657)
0.562
(0.447 to 0.673)
0.590
(0.477 to 0.697)
0.524
(0.412 to 0.634)
3.Secondary Outcome
Title Overall Survival
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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

Overall Number of Participants Analyzed 84 80 83 84
Median (90% Confidence Interval)
Unit of Measure: Months
28.6
(22.3 to 34.9)
24.7
(21.4 to 35.3)
27.5
(21.5 to 37.4)
24.3
(19.7 to 34.7)
4.Secondary Outcome
Title Objective Response Rate
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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

Overall Number of Participants Analyzed 84 80 83 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients
0.133
(0.068 to 0.225)
0.316
(0.216 to 0.431)
0.305
(0.208 to 0.416)
0.202
(0.123 to 0.304)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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 [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
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 [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
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 [Not Specified]
Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/88 (44.32%)   66/86 (76.74%)   74/90 (82.22%)   76/91 (83.52%) 
Blood and lymphatic system disorders         
Hemoglobin  1  0/88 (0.00%)  2/86 (2.33%)  2/90 (2.22%)  8/91 (8.79%) 
Cardiac disorders         
Atrial fibrillation  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Atrial flutter  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Sinus arrhythmia  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/91 (0.00%) 
Supraventricular tachycardia  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Cardiac-ischemia  1  1/88 (1.14%)  3/86 (3.49%)  1/90 (1.11%)  1/91 (1.10%) 
Left ventricular diastolic dysfunction  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Left ventricular systolic dysfunction  1  1/88 (1.14%)  2/86 (2.33%)  1/90 (1.11%)  0/91 (0.00%) 
Cardiac/heart, pain  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
Eye disorders         
Cataract  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Keratitis  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Gastrointestinal disorders         
Colitis  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Constipation  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Diarrhea w/o prior colostomy  1  0/88 (0.00%)  6/86 (6.98%)  6/90 (6.67%)  9/91 (9.89%) 
Enteritis  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Gastritis  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Ileus  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Muco/stomatitis by exam, oral cavity  1  0/88 (0.00%)  1/86 (1.16%)  3/90 (3.33%)  1/91 (1.10%) 
Muco/stomatitis (symptom) oral cavity  1  0/88 (0.00%)  2/86 (2.33%)  0/90 (0.00%)  3/91 (3.30%) 
Nausea  1  0/88 (0.00%)  1/86 (1.16%)  2/90 (2.22%)  0/91 (0.00%) 
Necrosis, colon/cecum/appendix  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Obstruction, colon  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/91 (0.00%) 
Perforation, colon  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Ulcer, anus  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Ulcer, gastric  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  1/91 (1.10%) 
Vomiting  1  0/88 (0.00%)  0/86 (0.00%)  2/90 (2.22%)  0/91 (0.00%) 
GI-other  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Rectum, hemorrhage  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Abdomen, pain  1  1/88 (1.14%)  3/86 (3.49%)  6/90 (6.67%)  4/91 (4.40%) 
Anus, pain  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Oral cavity, pain  1  1/88 (1.14%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Rectum, pain  1  0/88 (0.00%)  2/86 (2.33%)  0/90 (0.00%)  0/91 (0.00%) 
General disorders         
Fatigue  1  2/88 (2.27%)  13/86 (15.12%)  10/90 (11.11%)  14/91 (15.38%) 
Fever w/o neutropenia  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Edema limb  1  0/88 (0.00%)  3/86 (3.49%)  0/90 (0.00%)  0/91 (0.00%) 
Chest/thoracic pain NOS  1  0/88 (0.00%)  0/86 (0.00%)  2/90 (2.22%)  0/91 (0.00%) 
Immune system disorders         
Allergic reaction  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Infections and infestations         
Infection Gr0-2 neut, abdomen  1  0/88 (0.00%)  2/86 (2.33%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, anal/perianl  1  1/88 (1.14%)  0/86 (0.00%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, bone  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Infection Gr0-2 neut, dental-tooth  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, kidney  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, lung  1  0/88 (0.00%)  3/86 (3.49%)  0/90 (0.00%)  2/91 (2.20%) 
Infection Gr0-2 neut, rectum  1  0/88 (0.00%)  3/86 (3.49%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, salivary  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Infection Gr0-2 neut, sinus  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  1/91 (1.10%) 
Infection Gr0-2 neut, skin  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
Infection Gr0-2 neut, wound  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Infection w/ unk ANC lung  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Infection Gr0-2 neut, blood  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Investigations         
Leukocytes  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  4/91 (4.40%) 
Lymphopenia  1  0/88 (0.00%)  3/86 (3.49%)  2/90 (2.22%)  10/91 (10.99%) 
Neutrophils  1  0/88 (0.00%)  3/86 (3.49%)  0/90 (0.00%)  4/91 (4.40%) 
Platelets  1  0/88 (0.00%)  2/86 (2.33%)  1/90 (1.11%)  8/91 (8.79%) 
Cardiac troponin I (cTnI)  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Weight loss  1  0/88 (0.00%)  2/86 (2.33%)  3/90 (3.33%)  3/91 (3.30%) 
Alkaline phosphatase  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
ALT, SGPT  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  1/91 (1.10%) 
Amylase  1  0/88 (0.00%)  0/86 (0.00%)  2/90 (2.22%)  4/91 (4.40%) 
AST, SGOT  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Bilirubin  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Hypercholesterolemia  1  0/88 (0.00%)  4/86 (4.65%)  0/90 (0.00%)  5/91 (5.49%) 
Creatinine  1  0/88 (0.00%)  1/86 (1.16%)  3/90 (3.33%)  0/91 (0.00%) 
Lipase  1  1/88 (1.14%)  2/86 (2.33%)  4/90 (4.44%)  4/91 (4.40%) 
Vital capacity  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Metabolism and nutrition disorders         
Anorexia  1  2/88 (2.27%)  3/86 (3.49%)  4/90 (4.44%)  3/91 (3.30%) 
Dehydration  1  0/88 (0.00%)  5/86 (5.81%)  3/90 (3.33%)  1/91 (1.10%) 
Acidosis  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Hypoalbuminemia  1  0/88 (0.00%)  2/86 (2.33%)  0/90 (0.00%)  0/91 (0.00%) 
Hypocalcemia  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Hyperglycemia  1  0/88 (0.00%)  9/86 (10.47%)  2/90 (2.22%)  16/91 (17.58%) 
Hypoglycemia  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
Hypophosphatemia  1  2/88 (2.27%)  7/86 (8.14%)  10/90 (11.11%)  30/91 (32.97%) 
Hyperkalemia  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  2/91 (2.20%) 
Hypokalemia  1  0/88 (0.00%)  2/86 (2.33%)  3/90 (3.33%)  5/91 (5.49%) 
Hyponatremia  1  0/88 (0.00%)  3/86 (3.49%)  8/90 (8.89%)  4/91 (4.40%) 
Hypertriglyceridemia  1  0/88 (0.00%)  4/86 (4.65%)  0/90 (0.00%)  5/91 (5.49%) 
Hyperuricemia  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  1/91 (1.10%) 
Musculoskeletal and connective tissue disorders         
Nonneuropathic generalized weakness  1  0/88 (0.00%)  0/86 (0.00%)  2/90 (2.22%)  0/91 (0.00%) 
Back, pain  1  1/88 (1.14%)  1/86 (1.16%)  1/90 (1.11%)  3/91 (3.30%) 
Chest wall, pain  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Extremity-limb, pain  1  0/88 (0.00%)  1/86 (1.16%)  3/90 (3.33%)  0/91 (0.00%) 
Joint, pain  1  2/88 (2.27%)  2/86 (2.33%)  1/90 (1.11%)  2/91 (2.20%) 
Muscle, pain  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  2/91 (2.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Secondary malignancy  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Nervous system disorders         
CNS, hemorrhage  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
CNS cerebrovascular ischemia  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Dizziness  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Memory impairment  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Neuropathy-sensory  1  0/88 (0.00%)  1/86 (1.16%)  2/90 (2.22%)  0/91 (0.00%) 
Seizure  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Syncope  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Head/headache  1  2/88 (2.27%)  5/86 (5.81%)  4/90 (4.44%)  3/91 (3.30%) 
Neuropathic, pain  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Psychiatric disorders         
Confusion  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Anxiety  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  1/91 (1.10%) 
Depression  1  0/88 (0.00%)  0/86 (0.00%)  2/90 (2.22%)  0/91 (0.00%) 
Renal and urinary disorders         
Urinary hemorrhage NOS  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Glomerular filtration rate  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  0/91 (0.00%) 
Proteinuria  1  9/88 (10.23%)  22/86 (25.58%)  9/90 (10.00%)  1/91 (1.10%) 
Renal failure  1  0/88 (0.00%)  3/86 (3.49%)  2/90 (2.22%)  2/91 (2.20%) 
Respiratory, thoracic and mediastinal disorders         
Lung, hemorrhage  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Nose, hemorrhage  1  0/88 (0.00%)  2/86 (2.33%)  0/90 (0.00%)  0/91 (0.00%) 
Bronchospasm, wheezing  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Cough  1  0/88 (0.00%)  3/86 (3.49%)  0/90 (0.00%)  2/91 (2.20%) 
Dyspnea  1  0/88 (0.00%)  6/86 (6.98%)  1/90 (1.11%)  2/91 (2.20%) 
Nasal cavity/paranasal sinus reaction  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
Obstruction, airway-bronchus  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  0/91 (0.00%) 
Pleural effusion (non-malignant)  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  2/91 (2.20%) 
Pneumonitis/pulmonary infiltrates  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  4/91 (4.40%) 
Skin and subcutaneous tissue disorders         
Photosensitivity  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  1/91 (1.10%) 
Pruritus/itching  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  4/91 (4.40%) 
Rash/desquamation  1  1/88 (1.14%)  2/86 (2.33%)  3/90 (3.33%)  7/91 (7.69%) 
Rash: acne/acneiform  1  0/88 (0.00%)  1/86 (1.16%)  0/90 (0.00%)  2/91 (2.20%) 
Erythema multiforme  1  0/88 (0.00%)  0/86 (0.00%)  0/90 (0.00%)  1/91 (1.10%) 
Hand-foot reaction  1  0/88 (0.00%)  1/86 (1.16%)  20/90 (22.22%)  3/91 (3.30%) 
Ulceration  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Vascular disorders         
Hypertension  1  18/88 (20.45%)  15/86 (17.44%)  34/90 (37.78%)  7/91 (7.69%) 
Hypotension  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Thrombosis/thrombus/embolism  1  2/88 (2.27%)  4/86 (4.65%)  2/90 (2.22%)  2/91 (2.20%) 
Vascular-Other (Specify)  1  0/88 (0.00%)  0/86 (0.00%)  1/90 (1.11%)  0/91 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A (Bevacizumab) Arm B (Bevacizumab and Temsirolimus) Arm C (Bevacizumab and Sorafenib) Arm D (Sorafenib and Temsirolimus)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   80/88 (90.91%)   86/86 (100.00%)   89/90 (98.89%)   90/91 (98.90%) 
Blood and lymphatic system disorders         
Hemoglobin  1  30/88 (34.09%)  65/86 (75.58%)  37/90 (41.11%)  75/91 (82.42%) 
Eye disorders         
Tearing  1  0/88 (0.00%)  5/86 (5.81%)  1/90 (1.11%)  1/91 (1.10%) 
Gastrointestinal disorders         
Constipation  1  14/88 (15.91%)  24/86 (27.91%)  23/90 (25.56%)  24/91 (26.37%) 
Diarrhea w/o prior colostomy  1  15/88 (17.05%)  40/86 (46.51%)  45/90 (50.00%)  65/91 (71.43%) 
Dry mouth  1  1/88 (1.14%)  2/86 (2.33%)  2/90 (2.22%)  6/91 (6.59%) 
Flatulence  1  0/88 (0.00%)  1/86 (1.16%)  1/90 (1.11%)  7/91 (7.69%) 
Dyspepsia  1  5/88 (5.68%)  7/86 (8.14%)  19/90 (21.11%)  7/91 (7.69%) 
Muco/stomatitis by exam, oral cavity  1  2/88 (2.27%)  22/86 (25.58%)  20/90 (22.22%)  13/91 (14.29%) 
Muco/stomatitis (symptom) oral cavity  1  5/88 (5.68%)  40/86 (46.51%)  33/90 (36.67%)  24/91 (26.37%) 
Nausea  1  17/88 (19.32%)  37/86 (43.02%)  38/90 (42.22%)  50/91 (54.95%) 
Vomiting  1  7/88 (7.95%)  18/86 (20.93%)  23/90 (25.56%)  24/91 (26.37%) 
Abdomen, pain  1  4/88 (4.55%)  7/86 (8.14%)  15/90 (16.67%)  24/91 (26.37%) 
Oral cavity, pain  1  0/88 (0.00%)  6/86 (6.98%)  4/90 (4.44%)  4/91 (4.40%) 
General disorders         
Fatigue  1  48/88 (54.55%)  66/86 (76.74%)  64/90 (71.11%)  75/91 (82.42%) 
Fever w/o neutropenia  1  2/88 (2.27%)  11/86 (12.79%)  6/90 (6.67%)  13/91 (14.29%) 
Rigors/chills  1  5/88 (5.68%)  12/86 (13.95%)  7/90 (7.78%)  8/91 (8.79%) 
Edema head and neck  1  1/88 (1.14%)  5/86 (5.81%)  0/90 (0.00%)  6/91 (6.59%) 
Edema limb  1  5/88 (5.68%)  15/86 (17.44%)  11/90 (12.22%)  18/91 (19.78%) 
Chest/thoracic pain NOS  1  2/88 (2.27%)  9/86 (10.47%)  3/90 (3.33%)  5/91 (5.49%) 
Immune system disorders         
Allergic reaction  1  0/88 (0.00%)  5/86 (5.81%)  0/90 (0.00%)  4/91 (4.40%) 
Infections and infestations         
Infection Gr0-2 neut, sinus  1  1/88 (1.14%)  7/86 (8.14%)  3/90 (3.33%)  4/91 (4.40%) 
Investigations         
Leukocytes  1  4/88 (4.55%)  32/86 (37.21%)  12/90 (13.33%)  46/91 (50.55%) 
Lymphopenia  1  7/88 (7.95%)  21/86 (24.42%)  16/90 (17.78%)  28/91 (30.77%) 
Neutrophils  1  2/88 (2.27%)  21/86 (24.42%)  3/90 (3.33%)  22/91 (24.18%) 
Platelets  1  13/88 (14.77%)  43/86 (50.00%)  21/90 (23.33%)  52/91 (57.14%) 
Weight loss  1  7/88 (7.95%)  28/86 (32.56%)  31/90 (34.44%)  37/91 (40.66%) 
Alkaline phosphatase  1  9/88 (10.23%)  19/86 (22.09%)  19/90 (21.11%)  34/91 (37.36%) 
ALT, SGPT  1  11/88 (12.50%)  23/86 (26.74%)  11/90 (12.22%)  36/91 (39.56%) 
Amylase  1  5/88 (5.68%)  8/86 (9.30%)  11/90 (12.22%)  9/91 (9.89%) 
AST, SGOT  1  12/88 (13.64%)  26/86 (30.23%)  23/90 (25.56%)  39/91 (42.86%) 
Bilirubin  1  3/88 (3.41%)  0/86 (0.00%)  6/90 (6.67%)  6/91 (6.59%) 
Hypercholesterolemia  1  11/88 (12.50%)  39/86 (45.35%)  16/90 (17.78%)  34/91 (37.36%) 
Creatinine  1  25/88 (28.41%)  43/86 (50.00%)  37/90 (41.11%)  35/91 (38.46%) 
Lipase  1  7/88 (7.95%)  13/86 (15.12%)  23/90 (25.56%)  14/91 (15.38%) 
Metabolic/Laboratory-other  1  2/88 (2.27%)  10/86 (11.63%)  10/90 (11.11%)  8/91 (8.79%) 
Metabolism and nutrition disorders         
Anorexia  1  12/88 (13.64%)  46/86 (53.49%)  41/90 (45.56%)  48/91 (52.75%) 
Hypoalbuminemia  1  5/88 (5.68%)  23/86 (26.74%)  17/90 (18.89%)  17/91 (18.68%) 
Bicarbonate  1  1/88 (1.14%)  5/86 (5.81%)  1/90 (1.11%)  1/91 (1.10%) 
Hypocalcemia  1  5/88 (5.68%)  16/86 (18.60%)  12/90 (13.33%)  20/91 (21.98%) 
Hyperglycemia  1  12/88 (13.64%)  47/86 (54.65%)  30/90 (33.33%)  50/91 (54.95%) 
Hypomagnesemia  1  1/88 (1.14%)  1/86 (1.16%)  0/90 (0.00%)  5/91 (5.49%) 
Hypophosphatemia  1  6/88 (6.82%)  21/86 (24.42%)  29/90 (32.22%)  53/91 (58.24%) 
Hyperkalemia  1  5/88 (5.68%)  6/86 (6.98%)  10/90 (11.11%)  5/91 (5.49%) 
Hypokalemia  1  5/88 (5.68%)  14/86 (16.28%)  7/90 (7.78%)  17/91 (18.68%) 
Hyponatremia  1  7/88 (7.95%)  8/86 (9.30%)  19/90 (21.11%)  20/91 (21.98%) 
Hypertriglyceridemia  1  17/88 (19.32%)  39/86 (45.35%)  29/90 (32.22%)  42/91 (46.15%) 
Musculoskeletal and connective tissue disorders         
Back, pain  1  4/88 (4.55%)  11/86 (12.79%)  4/90 (4.44%)  8/91 (8.79%) 
Extremity-limb, pain  1  2/88 (2.27%)  3/86 (3.49%)  8/90 (8.89%)  7/91 (7.69%) 
Joint, pain  1  10/88 (11.36%)  18/86 (20.93%)  16/90 (17.78%)  15/91 (16.48%) 
Muscle, pain  1  2/88 (2.27%)  5/86 (5.81%)  9/90 (10.00%)  7/91 (7.69%) 
Nervous system disorders         
Taste disturbance  1  5/88 (5.68%)  29/86 (33.72%)  24/90 (26.67%)  35/91 (38.46%) 
Dizziness  1  1/88 (1.14%)  3/86 (3.49%)  7/90 (7.78%)  3/91 (3.30%) 
Neuropathy-sensory  1  2/88 (2.27%)  10/86 (11.63%)  20/90 (22.22%)  11/91 (12.09%) 
Head/headache  1  13/88 (14.77%)  28/86 (32.56%)  23/90 (25.56%)  22/91 (24.18%) 
Psychiatric disorders         
Insomnia  1  1/88 (1.14%)  7/86 (8.14%)  7/90 (7.78%)  10/91 (10.99%) 
Depression  1  4/88 (4.55%)  13/86 (15.12%)  6/90 (6.67%)  10/91 (10.99%) 
Renal and urinary disorders         
Glomerular filtration rate  1  3/88 (3.41%)  5/86 (5.81%)  6/90 (6.67%)  1/91 (1.10%) 
Proteinuria  1  25/88 (28.41%)  40/86 (46.51%)  45/90 (50.00%)  2/91 (2.20%) 
Respiratory, thoracic and mediastinal disorders         
Allergic rhinitis  1  9/88 (10.23%)  10/86 (11.63%)  9/90 (10.00%)  5/91 (5.49%) 
Nose, hemorrhage  1  18/88 (20.45%)  36/86 (41.86%)  29/90 (32.22%)  22/91 (24.18%) 
Throat/pharynx/larynx, pain  1  0/88 (0.00%)  4/86 (4.65%)  5/90 (5.56%)  1/91 (1.10%) 
Cough  1  7/88 (7.95%)  22/86 (25.58%)  9/90 (10.00%)  16/91 (17.58%) 
Dyspnea  1  8/88 (9.09%)  30/86 (34.88%)  13/90 (14.44%)  21/91 (23.08%) 
Pneumonitis/pulmonary infiltrates  1  0/88 (0.00%)  8/86 (9.30%)  0/90 (0.00%)  4/91 (4.40%) 
Voice changes/dysarthria  1  9/88 (10.23%)  12/86 (13.95%)  30/90 (33.33%)  11/91 (12.09%) 
Skin and subcutaneous tissue disorders         
Dry skin  1  11/88 (12.50%)  21/86 (24.42%)  30/90 (33.33%)  30/91 (32.97%) 
Alopecia  1  3/88 (3.41%)  10/86 (11.63%)  13/90 (14.44%)  14/91 (15.38%) 
Nail changes  1  5/88 (5.68%)  13/86 (15.12%)  13/90 (14.44%)  16/91 (17.58%) 
Pruritus/itching  1  6/88 (6.82%)  27/86 (31.40%)  9/90 (10.00%)  29/91 (31.87%) 
Rash/desquamation  1  3/88 (3.41%)  35/86 (40.70%)  16/90 (17.78%)  41/91 (45.05%) 
Rash: acne/acneiform  1  3/88 (3.41%)  36/86 (41.86%)  14/90 (15.56%)  39/91 (42.86%) 
Hand-foot reaction  1  3/88 (3.41%)  15/86 (17.44%)  43/90 (47.78%)  26/91 (28.57%) 
Vascular disorders         
Hypertension  1  29/88 (32.95%)  39/86 (45.35%)  42/90 (46.67%)  34/91 (37.36%) 
Hypotension  1  0/88 (0.00%)  5/86 (5.81%)  4/90 (4.44%)  1/91 (1.10%) 
Flushing  1  0/88 (0.00%)  1/86 (1.16%)  5/90 (5.56%)  4/91 (4.40%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
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: Study Statistician
Organization: ECOG-ACRIN Statistical Office
Phone: 617-632-3012
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00378703     History of Changes
Other Study ID Numbers: NCI-2009-00533
NCI-2009-00533 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ECOG-E2804
CDR0000499788
E2804 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
E2804 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: September 19, 2006
First Posted: September 21, 2006
Results First Submitted: April 14, 2015
Results First Posted: May 5, 2015
Last Update Posted: November 14, 2018