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Trial record 7 of 21 for:    "Adenoma" | "Sirolimus"

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01010126
Recruitment Status : Completed
First Posted : November 9, 2009
Results First Posted : January 25, 2019
Last Update Posted : January 25, 2019
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 Adult Hepatocellular Carcinoma
Advanced Adult Hepatocellular Carcinoma
Endometrial Serous Adenocarcinoma
Localized Non-Resectable Adult Liver Carcinoma
Lung Carcinoid Tumor
Malignant Pancreatic Gastrinoma
Malignant Pancreatic Glucagonoma
Malignant Pancreatic Insulinoma
Malignant Pancreatic Somatostatinoma
Metastatic Digestive System Neuroendocrine Tumor G1
Ovarian Carcinosarcoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Seromucinous Carcinoma
Ovarian Serous Surface Papillary Adenocarcinoma
Pancreatic Alpha Cell Adenoma
Pancreatic Beta Cell Adenoma
Pancreatic Delta Cell Adenoma
Pancreatic G-Cell Adenoma
Pancreatic Polypeptide Tumor
Recurrent Adult Liver Carcinoma
Recurrent Digestive System Neuroendocrine Tumor G1
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Pancreatic Neuroendocrine Carcinoma
Recurrent Primary Peritoneal Carcinoma
Recurrent Uterine Corpus Carcinoma
Regional Digestive System Neuroendocrine Tumor G1
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Cancer
Stage IIIA Primary Peritoneal Cancer
Stage IIIA Uterine Corpus Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Cancer
Stage IIIB Primary Peritoneal Cancer
Stage IIIB Uterine Corpus Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Cancer
Stage IIIC Primary Peritoneal Cancer
Stage IIIC Uterine Corpus Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Cancer
Stage IV Primary Peritoneal Cancer
Stage IVA Uterine Corpus Cancer
Stage IVB Uterine Corpus Cancer
Uterine Carcinosarcoma
Interventions Biological: Bevacizumab
Drug: Temsirolimus
Enrollment 252
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 27 58 28 57 58 24
Completed 26 58 27 57 55 24
Not Completed 1 0 1 0 3 0
Reason Not Completed
Withdrawal by Subject             1             0             1             0             3             0
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort Total
Hide Arm/Group Description Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 26 58 27 57 58 24 250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 26 participants 58 participants 27 participants 57 participants 58 participants 24 participants 250 participants
60
(40 to 80)
62.5
(35 to 82)
59
(31 to 74)
62
(35 to 89)
58.5
(29 to 81)
54.5
(40 to 78)
60
(29 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 58 participants 27 participants 57 participants 58 participants 24 participants 250 participants
Female
26
 100.0%
58
 100.0%
5
  18.5%
31
  54.4%
29
  50.0%
10
  41.7%
159
  63.6%
Male
0
   0.0%
0
   0.0%
22
  81.5%
26
  45.6%
29
  50.0%
14
  58.3%
91
  36.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 58 participants 27 participants 57 participants 58 participants 24 participants 250 participants
Hispanic or Latino
4
  15.4%
2
   3.4%
2
   7.4%
0
   0.0%
1
   1.7%
2
   8.3%
11
   4.4%
Not Hispanic or Latino
19
  73.1%
54
  93.1%
25
  92.6%
54
  94.7%
57
  98.3%
22
  91.7%
231
  92.4%
Unknown or Not Reported
3
  11.5%
2
   3.4%
0
   0.0%
3
   5.3%
0
   0.0%
0
   0.0%
8
   3.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 58 participants 27 participants 57 participants 58 participants 24 participants 250 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
5
   8.6%
3
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
8
   3.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.8%
0
   0.0%
0
   0.0%
1
   0.4%
Black or African American
3
  11.5%
2
   3.4%
2
   7.4%
6
  10.5%
8
  13.8%
3
  12.5%
24
   9.6%
White
22
  84.6%
49
  84.5%
22
  81.5%
49
  86.0%
50
  86.2%
20
  83.3%
212
  84.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.8%
2
   3.4%
0
   0.0%
1
   1.8%
0
   0.0%
1
   4.2%
5
   2.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 58 participants 27 participants 57 participants 58 participants 24 participants 250 participants
Canada 5 34 8 2 14 0 63
United States 21 24 19 55 44 24 187
1.Primary Outcome
Title Progression Free Survival Rate
Hide Description Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The 6-month progression free survival rate is the proportion of evaluable patients progression-free 6 months from registration. The 6-month progression-free rate is defined as the total number of efficacy evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of evaluable patients enrolled on study. Kaplan-Meier methodology will be used to estimate the final success proportion (i.e. progression free at 6 months with a 95% confidence interval).
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that received study treatment and were evaluated for response are included in this analysis
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 55 54 24
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of patients
0.52
(0.35 to 0.77)
0.40
(0.29 to 0.55)
0.71
(0.54 to 0.94)
0.84
(0.75 to 0.95)
0.85
(0.75 to 0.95)
0.87
(0.74 to 1.00)
2.Primary Outcome
Title Tumor Response Rate
Hide Description Tumor response rate defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of efficacy evaluable patients enrolled on study. Patients were evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. In brief, a Complete Response (CR) means the complete disappearance of all target lesions and a reduction in each lymph node to <1 cm. A Partial Response (PR) is defined as a 30% decrease in the sum of the longest diameter of the non-nodal target lesion from baseline. Each requires no new lesions present at evaluation. The proportion of participants with a response is provided here for each cohort. The proportion was calculated as the number of patients that had a best response of CR or PR divided by the number of patients evaluated for a response in each cohort.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
For this analysis, the number of patients that had a best response of CR or PR were divided by the number of patients evaluated for a response.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 57 58 24
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.31
(0.14 to 0.52)
0.31
(0.20 to 0.45)
0.19
(0.06 to 0.38)
0.12
(0.05 to 0.24)
0.40
(0.27 to 0.53)
0.17
(0.05 to 0.37)
3.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is defined for all evaluable patients who have achieved a response as the date at which the patient’s objective status is first noted to be either a CR or PR to the date progression is documented. Objective response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) as described in Primary Objective 2 in this report. Median duration of response and the confidence interval for the median duration will be computed.
Time Frame Time from date at which the patient’s objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression is documented, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that were assessed as a Complete Response or Partial Response were included in this analysis.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 8 18 5 7 23 4
Median (95% Confidence Interval)
Unit of Measure: months
25.1
(0 to 35.5)
6.4
(3.7 to 10.8)
6.4
(0 to 11.1)
15.0
(0 to 18.8)
11.3
(8.8 to 21.2)
10.9
(3.7 to 34.1)
4.Secondary Outcome
Title Incidence of Adverse Events
Hide Description Adverse events are defined as events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. The number of patients reporting grade 3 or higher adverse events at least possibly related to treatment are reported here. For a complete list of all reported adverse events, please see the adverse events section of this report.
Time Frame Every cycle of treatment, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that received protocol treatment and were evaluated for adverse events are reported in this analysis.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 57 55 24
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3 Adverse Event
17
  65.4%
32
  55.2%
24
  88.9%
32
  56.1%
36
  65.5%
13
  54.2%
Grade 4 Adverse Event
1
   3.8%
6
  10.3%
0
   0.0%
6
  10.5%
8
  14.5%
0
   0.0%
Grade 5 Adverse Event
1
   3.8%
0
   0.0%
1
   3.7%
2
   3.5%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Overall Survival
Hide Description Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method.
Time Frame Time from registration to death, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that received study intervention and were followed for survival were included in this analysis.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 57 58 24
Median (95% Confidence Interval)
Unit of Measure: months
11.5 [1] 
(6.5 to NA)
16.3
(11.1 to 21.9)
14.8
(9.7 to 18.1)
32.7
(25.2 to 38.3)
35.0 [1] 
(14.6 to NA)
NA [2] 
(30.6 to NA)
[1]
Too few deaths occurred to estimate an upper 95% CI.
[2]
Too few deaths occurred to estimate a median or an upper 95% CI.
6.Secondary Outcome
Title Time to Disease Progression
Hide Description Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for evaluation, that patient will be censored for progression of disease at day one post-registration.
Time Frame Time from registration to disease progression, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that began protocol treatment and were evaluated for response are included in this analysis.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 55 54 24
Median (95% Confidence Interval)
Unit of Measure: months
6.0
(2.5 to 9.8)
5.6
(4.3 to 6.4)
8.0
(5.8 to 10.9)
15.2
(11.4 to 24.2)
13.1
(11.2 to 16.6)
18.0
(10.6 to 37.0)
7.Secondary Outcome
Title Time to Treatment Failure
Hide Description Time to treatment failure is defined as the time from study entry to the date patients end treatment.Time to treatment failure will be evaluated using the method of Kaplan-Meier.
Time Frame Time from study entry to the date patients end treatment, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that began study treatment were included in this analysis.
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description:
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 26 58 27 55 54 24
Median (95% Confidence Interval)
Unit of Measure: months
3.8
(2.3 to 6.4)
4.5
(2.7 to 5.6)
6.5
(2.3 to 8.0)
5.5
(4.4 to 8.1)
11.3
(8.6 to 13.3)
11.8
(5.8 to 18.0)
Time Frame Adverse events were collected at the end of each 28 day cycle for a maximum of 58 cycles.
Adverse Event Reporting Description Adverse events were collected at the end of each 28 day cycle for a maximum of 58 cycles.
 
Arm/Group Title Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Hide Arm/Group Description Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/26 (7.69%)      1/58 (1.72%)      3/27 (11.11%)      3/57 (5.26%)      0/55 (0.00%)      0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/26 (61.54%)      34/58 (58.62%)      13/27 (48.15%)      36/57 (63.16%)      27/55 (49.09%)      6/24 (25.00%)    
Blood and lymphatic system disorders             
Disseminated intravascular coagulation  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Hemoglobin decreased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 4/57 (7.02%)  5 2/55 (3.64%)  3 0/24 (0.00%)  0
Cardiac disorders             
Arrhythmia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  1
Atrial fibrillation  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Cardiac disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 2/55 (3.64%)  2 1/24 (4.17%)  1
Cardiac pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Left ventricular dysfunction  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Left ventricular failure  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Myocardial ischemia  1  0/26 (0.00%)  0 2/58 (3.45%)  2 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Palpitations  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders             
Abdominal distension  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Abdominal pain  1  2/26 (7.69%)  2 5/58 (8.62%)  7 3/27 (11.11%)  3 8/57 (14.04%)  10 6/55 (10.91%)  6 0/24 (0.00%)  0
Anal fistula  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Anal pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Anal ulcer  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Colitis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Colonic obstruction  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Colonic perforation  1  0/26 (0.00%)  0 3/58 (5.17%)  3 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Constipation  1  1/26 (3.85%)  2 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 3/55 (5.45%)  3 0/24 (0.00%)  0
Diarrhea  1  1/26 (3.85%)  1 1/58 (1.72%)  1 1/27 (3.70%)  1 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Dry mouth  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Duodenal hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Duodenal perforation  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Dyspepsia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Ear, nose and throat examination abnormal  1  0/26 (0.00%)  0 2/58 (3.45%)  2 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Esophageal hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 1/24 (4.17%)  2
Esophageal ulcer  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  2
Esophagitis  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  2
Gastritis  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorder  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 3/57 (5.26%)  3 1/55 (1.82%)  1 0/24 (0.00%)  0
Hemorrhoids  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Ileus  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Lower gastrointestinal hemorrhage  1  1/26 (3.85%)  1 0/58 (0.00%)  0 1/27 (3.70%)  1 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Nausea  1  1/26 (3.85%)  1 4/58 (6.90%)  4 2/27 (7.41%)  2 3/57 (5.26%)  4 2/55 (3.64%)  2 0/24 (0.00%)  0
Obstruction gastric  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Oral pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Rectal fistula  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Rectal hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Rectal pain  1  2/26 (7.69%)  2 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Small intestinal obstruction  1  1/26 (3.85%)  1 2/58 (3.45%)  2 0/27 (0.00%)  0 4/57 (7.02%)  5 0/55 (0.00%)  0 1/24 (4.17%)  1
Small intestinal perforation  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Upper gastrointestinal hemorrhage  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 0/57 (0.00%)  0 2/55 (3.64%)  2 0/24 (0.00%)  0
Vomiting  1  2/26 (7.69%)  2 4/58 (6.90%)  5 1/27 (3.70%)  1 1/57 (1.75%)  1 1/55 (1.82%)  1 1/24 (4.17%)  1
General disorders             
Chest pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Chills  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Disease progression  1  1/26 (3.85%)  1 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Edema limbs  1  0/26 (0.00%)  0 1/58 (1.72%)  2 1/27 (3.70%)  1 1/57 (1.75%)  1 2/55 (3.64%)  2 0/24 (0.00%)  0
Fatigue  1  0/26 (0.00%)  0 2/58 (3.45%)  2 4/27 (14.81%)  4 3/57 (5.26%)  4 1/55 (1.82%)  1 0/24 (0.00%)  0
Fever  1  0/26 (0.00%)  0 3/58 (5.17%)  3 1/27 (3.70%)  1 2/57 (3.51%)  2 2/55 (3.64%)  2 0/24 (0.00%)  0
Ill-defined disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Multi-organ failure  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Pain  1  1/26 (3.85%)  1 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Sudden death  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Visceral edema  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  1
Hepatobiliary disorders             
Hepatic hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations             
Abdominal infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Anal infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Anorectal infection  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Biliary tract infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Catheter related infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Colitis, infectious (e.g., Clostridium difficile)  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Gallbladder infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Pneumonia  1  0/26 (0.00%)  0 2/58 (3.45%)  2 1/27 (3.70%)  1 1/57 (1.75%)  1 3/55 (5.45%)  3 0/24 (0.00%)  0
Sepsis  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Skin infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Urinary tract infection  1  2/26 (7.69%)  2 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Wound infection  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Injury, poisoning and procedural complications             
Fracture  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Postoperative hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Rectal anastomotic leak  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Investigations             
Activated partial thromboplastin time prolonged  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Alanine aminotransferase increased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Alkaline phosphatase increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Aspartate aminotransferase increased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Bilirubin increased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Creatinine increased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
INR increased  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Laboratory test abnormal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Leukocyte count decreased  1  0/26 (0.00%)  0 2/58 (3.45%)  2 1/27 (3.70%)  1 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Lymphocyte count decreased  1  1/26 (3.85%)  1 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  3 0/24 (0.00%)  0
Neutrophil count decreased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Platelet count decreased  1  0/26 (0.00%)  0 3/58 (5.17%)  3 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Serum cholesterol increased  1  2/26 (7.69%)  2 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Weight gain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Weight loss  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Metabolism and nutrition disorders             
Anorexia  1  1/26 (3.85%)  1 1/58 (1.72%)  1 0/27 (0.00%)  0 2/57 (3.51%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Blood glucose increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 3/55 (5.45%)  3 0/24 (0.00%)  0
Dehydration  1  2/26 (7.69%)  2 3/58 (5.17%)  3 1/27 (3.70%)  2 5/57 (8.77%)  6 1/55 (1.82%)  1 0/24 (0.00%)  0
Serum albumin decreased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  2 0/24 (0.00%)  0
Serum glucose decreased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Serum phosphate decreased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Serum potassium decreased  1  0/26 (0.00%)  0 3/58 (5.17%)  3 1/27 (3.70%)  1 2/57 (3.51%)  3 3/55 (5.45%)  3 0/24 (0.00%)  0
Serum potassium increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Serum sodium decreased  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 0/57 (0.00%)  0 3/55 (5.45%)  4 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Bone pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Buttock pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Joint effusion  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Joint pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  1
Muscle weakness  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 3/57 (5.26%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Musculoskeletal disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Pain in extremity  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Nervous system disorders             
Cognitive disturbance  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Depressed level of consciousness  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Dizziness  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  2 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Headache  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 2/55 (3.64%)  2 0/24 (0.00%)  0
Intracranial hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Ischemia cerebrovascular  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Leukoencephalopathy  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Memory impairment  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Neurological disorder NOS  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Peripheral sensory neuropathy  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Syncope  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  2 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Psychiatric disorders             
Confusion  1  0/26 (0.00%)  0 0/58 (0.00%)  0 3/27 (11.11%)  5 2/57 (3.51%)  3 1/55 (1.82%)  1 0/24 (0.00%)  0
Depression  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Psychosis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Renal and urinary disorders             
Protein urine positive  1  2/26 (7.69%)  3 2/58 (3.45%)  4 0/27 (0.00%)  0 0/57 (0.00%)  0 2/55 (3.64%)  3 1/24 (4.17%)  1
Renal failure  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  1 2/55 (3.64%)  2 0/24 (0.00%)  0
Urinary incontinence  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Urogenital disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Reproductive system and breast disorders             
Female genital tract fistula  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Vaginal discharge  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Vaginal fistula  1  0/26 (0.00%)  0 3/58 (5.17%)  3 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Dyspnea  1  2/26 (7.69%)  3 1/58 (1.72%)  1 1/27 (3.70%)  1 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Hemorrhage nasal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Hypoxia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Nasal congestion  1  0/26 (0.00%)  0 2/58 (3.45%)  3 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Pleural effusion  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Pneumonitis  1  0/26 (0.00%)  0 2/58 (3.45%)  2 1/27 (3.70%)  1 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Pulmonary hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Respiratory disorder  1  1/26 (3.85%)  1 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Skin and subcutaneous tissue disorders             
Decubitus ulcer  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Pain of skin  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Rash desquamating  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Skin disorder  1  1/26 (3.85%)  1 1/58 (1.72%)  2 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Skin ulceration  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Vascular disorders             
Hypertension  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  1 4/55 (7.27%)  4 0/24 (0.00%)  0
Hypotension  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Thrombosis  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Visceral arterial ischemia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
1
Term from vocabulary, MedDRA 9
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Endometrial Cohort Ovarian Cohort Hepatocellular Cohort Carcinoid Cohort Islet Cell (Double Agent) Cohort Islet Cell (Bevacizumab-only) Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/26 (100.00%)      58/58 (100.00%)      27/27 (100.00%)      56/57 (98.25%)      55/55 (100.00%)      24/24 (100.00%)    
Blood and lymphatic system disorders             
Blood disorder  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Hemoglobin decreased  1  20/26 (76.92%)  79 48/58 (82.76%)  212 23/27 (85.19%)  122 49/57 (85.96%)  382 49/55 (89.09%)  556 8/24 (33.33%)  82
Hemolysis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  9 1/55 (1.82%)  10 0/24 (0.00%)  0
Lymph node pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Lymphatic disorder  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Cardiac disorders             
Arrhythmia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Atrial fibrillation  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  13 0/24 (0.00%)  0
Atrial tachycardia  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Atrioventricular block complete  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  7 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Cardiac disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Cardiac pain  1  0/26 (0.00%)  0 2/58 (3.45%)  2 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Palpitations  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Pericardial effusion  1  1/26 (3.85%)  2 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Ear and labyrinth disorders             
External ear pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 3/57 (5.26%)  3 1/55 (1.82%)  3 0/24 (0.00%)  0
Hearing loss  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  5 0/24 (0.00%)  0
Hearing test abnormal  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Middle ear inflammation  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Tinnitus  1  0/26 (0.00%)  0 1/58 (1.72%)  8 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  7 0/24 (0.00%)  0
Eye disorders             
Cataract  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Dry eye syndrome  1  0/26 (0.00%)  0 2/58 (3.45%)  3 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Eye disorder  1  1/26 (3.85%)  45 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Eye pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Flashing vision  1  0/26 (0.00%)  0 1/58 (1.72%)  3 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Retinal detachment  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Vision blurred  1  1/26 (3.85%)  1 3/58 (5.17%)  8 0/27 (0.00%)  0 2/57 (3.51%)  8 2/55 (3.64%)  2 0/24 (0.00%)  0
Watering eyes  1  4/26 (15.38%)  13 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders             
Abdominal distension  1  1/26 (3.85%)  1 3/58 (5.17%)  5 0/27 (0.00%)  0 3/57 (5.26%)  9 0/55 (0.00%)  0 0/24 (0.00%)  0
Abdominal pain  1  2/26 (7.69%)  2 13/58 (22.41%)  21 4/27 (14.81%)  8 11/57 (19.30%)  27 7/55 (12.73%)  19 1/24 (4.17%)  1
Anal fistula  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  2 1/57 (1.75%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Anal hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  4 0/24 (0.00%)  0
Anal mucositis  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Anal pain  1  0/26 (0.00%)  0 4/58 (6.90%)  4 0/27 (0.00%)  0 2/57 (3.51%)  2 1/55 (1.82%)  5 1/24 (4.17%)  1
Anal ulcer  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Ascites  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Cheilitis  1  1/26 (3.85%)  4 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  4 0/24 (0.00%)  0
Constipation  1  7/26 (26.92%)  25 11/58 (18.97%)  16 3/27 (11.11%)  5 7/57 (12.28%)  10 9/55 (16.36%)  17 2/24 (8.33%)  2
Diarrhea  1  9/26 (34.62%)  36 18/58 (31.03%)  39 7/27 (25.93%)  20 33/57 (57.89%)  113 21/55 (38.18%)  73 5/24 (20.83%)  20
Dry mouth  1  4/26 (15.38%)  10 4/58 (6.90%)  28 1/27 (3.70%)  3 5/57 (8.77%)  24 1/55 (1.82%)  3 0/24 (0.00%)  0
Dyspepsia  1  2/26 (7.69%)  5 5/58 (8.62%)  6 2/27 (7.41%)  6 4/57 (7.02%)  12 2/55 (3.64%)  2 1/24 (4.17%)  1
Dysphagia  1  2/26 (7.69%)  6 2/58 (3.45%)  5 0/27 (0.00%)  0 1/57 (1.75%)  1 3/55 (5.45%)  15 0/24 (0.00%)  0
Ear, nose and throat examination abnormal  1  12/26 (46.15%)  31 18/58 (31.03%)  44 4/27 (14.81%)  6 28/57 (49.12%)  76 33/55 (60.00%)  116 3/24 (12.50%)  23
Esophageal mucositis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Esophageal pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  2 0/24 (0.00%)  0
Fecal incontinence  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Flatulence  1  1/26 (3.85%)  2 0/58 (0.00%)  0 0/27 (0.00%)  0 3/57 (5.26%)  7 2/55 (3.64%)  2 0/24 (0.00%)  0
Gastric mucositis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Gastritis  1  1/26 (3.85%)  1 1/58 (1.72%)  4 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorder  1  1/26 (3.85%)  3 3/58 (5.17%)  6 1/27 (3.70%)  1 7/57 (12.28%)  7 5/55 (9.09%)  8 2/24 (8.33%)  2
Gastroscopy abnormal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Gingival pain  1  0/26 (0.00%)  0 3/58 (5.17%)  15 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  3 0/24 (0.00%)  0
Hemorrhoids  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 10/57 (17.54%)  15 4/55 (7.27%)  8 0/24 (0.00%)  0
Lip pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  6 0/55 (0.00%)  0 0/24 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 4/57 (7.02%)  9 2/55 (3.64%)  3 0/24 (0.00%)  0
Mucositis oral  1  5/26 (19.23%)  13 27/58 (46.55%)  86 11/27 (40.74%)  27 17/57 (29.82%)  25 12/55 (21.82%)  43 2/24 (8.33%)  2
Nausea  1  11/26 (42.31%)  63 24/58 (41.38%)  49 9/27 (33.33%)  22 23/57 (40.35%)  63 22/55 (40.00%)  69 4/24 (16.67%)  13
Oesophagoscopy abnormal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 1/57 (1.75%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Oral hemorrhage  1  1/26 (3.85%)  2 3/58 (5.17%)  10 1/27 (3.70%)  1 1/57 (1.75%)  1 2/55 (3.64%)  8 0/24 (0.00%)  0
Oral pain  1  5/26 (19.23%)  6 5/58 (8.62%)  6 2/27 (7.41%)  4 7/57 (12.28%)  17 3/55 (5.45%)  13 0/24 (0.00%)  0
Periodontal disease  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Rectal fistula  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Rectal hemorrhage  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Rectal pain  1  1/26 (3.85%)  3 4/58 (6.90%)  4 1/27 (3.70%)  2 5/57 (8.77%)  10 2/55 (3.64%)  3 0/24 (0.00%)  0
Rectal ulcer  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Small intestinal obstruction  1  0/26 (0.00%)  0 1/58 (1.72%)  2 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Stomach pain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  4 2/55 (3.64%)  2 0/24 (0.00%)  0
Tooth disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Toothache  1  1/26 (3.85%)  1 2/58 (3.45%)  3 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Upper gastrointestinal hemorrhage  1  3/26 (11.54%)  3 2/58 (3.45%)  2 4/27 (14.81%)  8 5/57 (8.77%)  12 8/55 (14.55%)  21 0/24 (0.00%)  0
Vomiting  1  7/26 (26.92%)  10 8/58 (13.79%)  13 5/27 (18.52%)  8 13/57 (22.81%)  24 17/55 (30.91%)  26 3/24 (12.50%)  5
General disorders             
Chest pain  1  1/26 (3.85%)  2 1/58 (1.72%)  1 2/27 (7.41%)  3 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Chills  1  3/26 (11.54%)  4 5/58 (8.62%)  12 0/27 (0.00%)  0 4/57 (7.02%)  7 2/55 (3.64%)  2 0/24 (0.00%)  0
Edema limbs  1  5/26 (19.23%)  22 8/58 (13.79%)  25 3/27 (11.11%)  8 12/57 (21.05%)  55 15/55 (27.27%)  70 2/24 (8.33%)  2
Facial pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Fatigue  1  21/26 (80.77%)  120 43/58 (74.14%)  152 14/27 (51.85%)  67 40/57 (70.18%)  236 48/55 (87.27%)  293 12/24 (50.00%)  70
Fever  1  0/26 (0.00%)  0 4/58 (6.90%)  4 3/27 (11.11%)  4 5/57 (8.77%)  6 4/55 (7.27%)  4 1/24 (4.17%)  1
Flu-like symptoms  1  2/26 (7.69%)  2 1/58 (1.72%)  3 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  3 1/24 (4.17%)  1
Gait abnormal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  2
General symptom  1  2/26 (7.69%)  2 0/58 (0.00%)  0 1/27 (3.70%)  1 3/57 (5.26%)  8 2/55 (3.64%)  15 0/24 (0.00%)  0
Ill-defined disorder  1  1/26 (3.85%)  4 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Injection site reaction  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Localized edema  1  0/26 (0.00%)  0 2/58 (3.45%)  7 1/27 (3.70%)  1 2/57 (3.51%)  4 2/55 (3.64%)  3 0/24 (0.00%)  0
Pain  1  4/26 (15.38%)  5 3/58 (5.17%)  7 1/27 (3.70%)  1 3/57 (5.26%)  31 11/55 (20.00%)  57 2/24 (8.33%)  2
Immune system disorders             
Hypersensitivity  1  0/26 (0.00%)  0 3/58 (5.17%)  3 2/27 (7.41%)  2 2/57 (3.51%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Immune system disorder  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations             
Bladder infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Bronchitis  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Eye infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Gingival infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Infection  1  1/26 (3.85%)  1 1/58 (1.72%)  1 4/27 (14.81%)  6 3/57 (5.26%)  3 3/55 (5.45%)  6 3/24 (12.50%)  3
Joint infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  2 0/24 (0.00%)  0
Lip infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  2 0/24 (0.00%)  0
Nail infection  1  2/26 (7.69%)  3 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Pelvic infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Pneumonia  1  1/26 (3.85%)  2 2/58 (3.45%)  2 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Sinusitis  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  6 1/24 (4.17%)  1
Skin infection  1  2/26 (7.69%)  3 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 3/55 (5.45%)  3 0/24 (0.00%)  0
Soft tissue infection  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Tooth infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  2 2/55 (3.64%)  5 0/24 (0.00%)  0
Upper respiratory infection  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Urinary tract infection  1  0/26 (0.00%)  0 3/58 (5.17%)  4 1/27 (3.70%)  1 2/57 (3.51%)  5 2/55 (3.64%)  3 0/24 (0.00%)  0
Vaginal infection  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 1/24 (4.17%)  1
Wound infection  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Injury, poisoning and procedural complications             
Bruising  1  1/26 (3.85%)  2 5/58 (8.62%)  9 0/27 (0.00%)  0 3/57 (5.26%)  9 4/55 (7.27%)  18 1/24 (4.17%)  2
Fracture  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Radiation recall reaction (dermatologic)  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  5 0/24 (0.00%)  0
Tracheal hemorrhage  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Wound dehiscence  1  0/26 (0.00%)  0 2/58 (3.45%)  2 0/27 (0.00%)  0 2/57 (3.51%)  8 2/55 (3.64%)  4 0/24 (0.00%)  0
Investigations             
Activated partial thromboplastin time prolonged  1  2/26 (7.69%)  2 1/58 (1.72%)  1 0/27 (0.00%)  0 4/57 (7.02%)  6 3/55 (5.45%)  4 0/24 (0.00%)  0
Alanine aminotransferase increased  1  9/26 (34.62%)  28 14/58 (24.14%)  24 6/27 (22.22%)  33 18/57 (31.58%)  62 25/55 (45.45%)  113 3/24 (12.50%)  6
Alkaline phosphatase increased  1  7/26 (26.92%)  33 13/58 (22.41%)  24 3/27 (11.11%)  17 20/57 (35.09%)  114 19/55 (34.55%)  76 3/24 (12.50%)  22
Aspartate aminotransferase increased  1  11/26 (42.31%)  40 20/58 (34.48%)  43 8/27 (29.63%)  47 24/57 (42.11%)  100 31/55 (56.36%)  120 4/24 (16.67%)  9
Bilirubin increased  1  1/26 (3.85%)  2 2/58 (3.45%)  2 9/27 (33.33%)  21 14/57 (24.56%)  48 14/55 (25.45%)  40 1/24 (4.17%)  1
Creatinine increased  1  4/26 (15.38%)  20 9/58 (15.52%)  29 2/27 (7.41%)  7 18/57 (31.58%)  60 9/55 (16.36%)  42 4/24 (16.67%)  7
Fibrinogen decreased  1  0/26 (0.00%)  0 1/58 (1.72%)  2 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
INR increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 4/57 (7.02%)  8 1/55 (1.82%)  1 0/24 (0.00%)  0
Laboratory test abnormal  1  1/26 (3.85%)  1 1/58 (1.72%)  2 0/27 (0.00%)  0 4/57 (7.02%)  7 2/55 (3.64%)  2 0/24 (0.00%)  0
Leukocyte count decreased  1  10/26 (38.46%)  26 30/58 (51.72%)  108 16/27 (59.26%)  91 38/57 (66.67%)  158 34/55 (61.82%)  289 3/24 (12.50%)  12
Lipase increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Lymphocyte count decreased  1  6/26 (23.08%)  14 7/58 (12.07%)  11 6/27 (22.22%)  21 16/57 (28.07%)  72 19/55 (34.55%)  99 0/24 (0.00%)  0
Neutrophil count decreased  1  10/26 (38.46%)  15 25/58 (43.10%)  55 15/27 (55.56%)  54 21/57 (36.84%)  62 28/55 (50.91%)  130 3/24 (12.50%)  5
Platelet count decreased  1  16/26 (61.54%)  53 27/58 (46.55%)  86 22/27 (81.48%)  159 50/57 (87.72%)  327 41/55 (74.55%)  479 7/24 (29.17%)  52
Serum cholesterol increased  1  22/26 (84.62%)  147 38/58 (65.52%)  162 12/27 (44.44%)  49 38/57 (66.67%)  231 46/55 (83.64%)  408 7/24 (29.17%)  10
Weight gain  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 2/55 (3.64%)  2 0/24 (0.00%)  0
Weight loss  1  8/26 (30.77%)  15 9/58 (15.52%)  29 6/27 (22.22%)  30 20/57 (35.09%)  73 12/55 (21.82%)  38 2/24 (8.33%)  2
Metabolism and nutrition disorders             
Anorexia  1  16/26 (61.54%)  39 23/58 (39.66%)  59 8/27 (29.63%)  28 27/57 (47.37%)  72 29/55 (52.73%)  70 5/24 (20.83%)  14
Blood bicarbonate decreased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  3 0/55 (0.00%)  0 0/24 (0.00%)  0
Blood glucose increased  1  10/26 (38.46%)  43 14/58 (24.14%)  24 4/27 (14.81%)  7 30/57 (52.63%)  159 28/55 (50.91%)  138 11/24 (45.83%)  33
Dehydration  1  0/26 (0.00%)  0 2/58 (3.45%)  2 2/27 (7.41%)  2 1/57 (1.75%)  3 7/55 (12.73%)  8 0/24 (0.00%)  0
Glucose intolerance  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 1/55 (1.82%)  1 0/24 (0.00%)  0
Serum albumin decreased  1  3/26 (11.54%)  15 6/58 (10.34%)  7 3/27 (11.11%)  11 13/57 (22.81%)  37 13/55 (23.64%)  49 2/24 (8.33%)  2
Serum calcium decreased  1  3/26 (11.54%)  4 5/58 (8.62%)  10 2/27 (7.41%)  2 10/57 (17.54%)  23 11/55 (20.00%)  61 1/24 (4.17%)  1
Serum calcium increased  1  2/26 (7.69%)  2 1/58 (1.72%)  1 0/27 (0.00%)  0 2/57 (3.51%)  2 1/55 (1.82%)  1 6/24 (25.00%)  10
Serum glucose decreased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 3/57 (5.26%)  3 3/55 (5.45%)  3 1/24 (4.17%)  1
Serum magnesium decreased  1  1/26 (3.85%)  3 6/58 (10.34%)  8 1/27 (3.70%)  2 4/57 (7.02%)  9 1/55 (1.82%)  4 1/24 (4.17%)  1
Serum phosphate decreased  1  2/26 (7.69%)  3 4/58 (6.90%)  4 3/27 (11.11%)  3 10/57 (17.54%)  25 10/55 (18.18%)  22 1/24 (4.17%)  1
Serum potassium decreased  1  7/26 (26.92%)  10 10/58 (17.24%)  15 2/27 (7.41%)  2 25/57 (43.86%)  63 11/55 (20.00%)  25 3/24 (12.50%)  4
Serum potassium increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  3 4/57 (7.02%)  4 2/55 (3.64%)  2 5/24 (20.83%)  5
Serum sodium decreased  1  2/26 (7.69%)  2 5/58 (8.62%)  8 3/27 (11.11%)  4 6/57 (10.53%)  15 14/55 (25.45%)  42 5/24 (20.83%)  5
Serum sodium increased  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  3 0/24 (0.00%)  0
Serum triglycerides increased  1  16/26 (61.54%)  115 25/58 (43.10%)  73 7/27 (25.93%)  18 29/57 (50.88%)  176 32/55 (58.18%)  172 1/24 (4.17%)  1
Musculoskeletal and connective tissue disorders             
Arthritis  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Back pain  1  5/26 (19.23%)  12 5/58 (8.62%)  5 5/27 (18.52%)  5 3/57 (5.26%)  5 3/55 (5.45%)  3 0/24 (0.00%)  0
Buttock pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Chest wall pain  1  1/26 (3.85%)  1 1/58 (1.72%)  1 0/27 (0.00%)  0 1/57 (1.75%)  1 2/55 (3.64%)  3 0/24 (0.00%)  0
Joint disorder  1  0/26 (0.00%)  0 1/58 (1.72%)  1 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Joint effusion  1  1/26 (3.85%)  1 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Joint pain  1  5/26 (19.23%)  41 5/58 (8.62%)  7 2/27 (7.41%)  7 3/57 (5.26%)  4 3/55 (5.45%)  11 1/24 (4.17%)  1
Muscle weakness  1  0/26 (0.00%)  0 4/58 (6.90%)  7 0/27 (0.00%)  0 4/57 (7.02%)  4 3/55 (5.45%)  4 0/24 (0.00%)  0
Muscle weakness lower limb  1  0/26 (0.00%)  0 1/58 (1.72%)  3 1/27 (3.70%)  3 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Muscle weakness upper limb  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 0/55 (0.00%)  0 1/24 (4.17%)  1
Musculoskeletal disorder  1  0/26 (0.00%)  0 2/58 (3.45%)  2 0/27 (0.00%)  0 6/57 (10.53%)  11 6/55 (10.91%)  16 4/24 (16.67%)  6
Myalgia  1  2/26 (7.69%)  16 6/58 (10.34%)  9 0/27 (0.00%)  0 1/57 (1.75%)  5 8/55 (14.55%)  41 1/24 (4.17%)  2
Neck pain  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Pain in extremity  1  1/26 (3.85%)  2 5/58 (8.62%)  6 1/27 (3.70%)  5 4/57 (7.02%)  18 6/55 (10.91%)  10 2/24 (8.33%)  3
Nervous system disorders             
Depressed level of consciousness  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Dizziness  1  4/26 (15.38%)  6 7/58 (12.07%)  8 2/27 (7.41%)  4 3/57 (5.26%)  4 5/55 (9.09%)  13 2/24 (8.33%)  11
Glossopharyngeal nerve disorder  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  2 0/55 (0.00%)  0 0/24 (0.00%)  0
Headache  1  5/26 (19.23%)  39 23/58 (39.66%)  53 5/27 (18.52%)  11 20/57 (35.09%)  76 25/55 (45.45%)  117 6/24 (25.00%)  21
Leukoencephalopathy  1  1/26 (3.85%)  1 0/58 (0.00%)  0 1/27 (3.70%)  1 0/57 (0.00%)  0 0/55 (0.00%)  0 0/24 (0.00%)  0
Memory impairment  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 2/57 (3.51%)  3 1/55 (1.82%)  3 0/24 (0.00%)  0
Mini mental status examination abnormal  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 0/57 (0.00%)  0 1/55 (1.82%)  1 0/24 (0.00%)  0
Neurological disorder NOS  1  0/26 (0.00%)  0 0/58 (0.00%)  0 1/27 (3.70%)  1 3/57 (5.26%)  12 2/55 (3.64%)  2 1/24 (4.17%)  1
Peripheral motor neuropathy  1  0/26 (0.00%)  0 1/58 (1.72%)  1 1/27 (3.70%)  1 2/57 (3.51%)  2 1/55 (1.82%)  1 0/24 (0.00%)  0
Peripheral sensory neuropathy  1  3/26 (11.54%)  7 5/58 (8.62%)  10 3/27 (11.11%)  6 7/57 (12.28%)  14 3/55 (5.45%)  26 1/24 (4.17%)  1
Recurrent laryngeal nerve palsy  1  0/26 (0.00%)  0 0/58 (0.00%)  0 0/27 (0.00%)  0 1/57 (1.75%)  1 0/55 (0.00%)  0 0/24 (0.00%)  0
Sinus pain  1  0/26 (0.00%)  0