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Trial record 16 of 864 for:    LENALIDOMIDE AND Angiogenesis

A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate 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: NCT00942578
Recruitment Status : Completed
First Posted : July 21, 2009
Results First Posted : October 11, 2018
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Ravi A. Madan, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Prostate Cancer
Interventions Drug: Bevacizumab
Drug: Lenalidomide
Drug: Docetaxel
Drug: Prednisone
Enrollment 63
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Hide Arm/Group Description

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Period Title: Dose Escalation Phase
Started 3 3 3
Completed 3 3 3
Not Completed 0 0 0
Period Title: Expansion Phase
Started 11 0 43
Completed 11 0 43
Not Completed 0 0 0
Arm/Group Title 15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide Total
Hide Arm/Group Description

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Total of all reporting groups
Overall Number of Baseline Participants 14 3 46 63
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  57.1%
1
  33.3%
20
  43.5%
29
  46.0%
>=65 years
6
  42.9%
2
  66.7%
26
  56.5%
34
  54.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 3 participants 46 participants 63 participants
64.25  (5.9) 63.2  (4.95) 66.07  (8.02) 64.51  (6.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
14
 100.0%
3
 100.0%
46
 100.0%
63
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   2.2%
1
   1.6%
Not Hispanic or Latino
14
 100.0%
3
 100.0%
45
  97.8%
62
  98.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
   2.2%
1
   1.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   2.2%
1
   1.6%
Black or African American
3
  21.4%
1
  33.3%
14
  30.4%
18
  28.6%
White
11
  78.6%
2
  66.7%
30
  65.2%
43
  68.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 14 participants 3 participants 46 participants 63 participants
14
 100.0%
3
 100.0%
46
 100.0%
63
 100.0%
Gleason Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
≤6
1
   7.1%
0
   0.0%
3
   6.5%
4
   6.3%
7
3
  21.4%
1
  33.3%
11
  23.9%
15
  23.8%
8
4
  28.6%
1
  33.3%
10
  21.7%
15
  23.8%
9
4
  28.6%
1
  33.3%
18
  39.1%
23
  36.5%
10
2
  14.3%
0
   0.0%
4
   8.7%
6
   9.5%
[1]
Measure Description: The Gleason score helps the physician determine whether prostate tissue is normal or different than normal. The Gleason score ranges from 2-10. The lower number means the prostate tissue is normal tissue. The higher number means the prostate tissue is not normal tissue and may be cancer.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
0
3
  21.4%
0
   0.0%
7
  15.2%
10
  15.9%
1
11
  78.6%
3
 100.0%
36
  78.3%
50
  79.4%
2
0
   0.0%
0
   0.0%
3
   6.5%
3
   4.8%
[1]
Measure Description: ECOG 0 is defined as normal activity, fully active, able to carry on all pre-disease performance without restriction. ECOG 1 is defined as symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework. ECOG 2 is defined as in bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
Location of Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 46 participants 63 participants
Bone only
7
  50.0%
1
  33.3%
16
  34.8%
24
  38.1%
Bone and lymph nodes
1
   7.1%
2
  66.7%
24
  52.2%
27
  42.9%
Bone and visceral (3 hepatic)
4
  28.6%
0
   0.0%
3
   6.5%
7
  11.1%
Lymph node alone
1
   7.1%
0
   0.0%
2
   4.3%
3
   4.8%
Visceral alone ( bladder and lung)
1
   7.1%
0
   0.0%
1
   2.2%
2
   3.2%
Alkaline Phosphatase & Lactate Dehydrogenase   [1] 
Median (Full Range)
Unit of measure:  U/L
Number Analyzed 14 participants 3 participants 46 participants 63 participants
Alkaline phosphatase
124
(53 to 702)
84
(71 to 121)
127
(53 to 956)
125
(53 to 956)
Lactate dehydrogenase
209
(174 to 624)
177
(152 to 193)
206.5
(127 to 2305)
206
(127 to 2305)
[1]
Measure Description: Alkaline phosphatase is a test to assess liver disease and the normal range is 44 to 147 U/L.
Prostatic Specific Antigen (PSA)   [1] 
Median (Full Range)
Unit of measure:  U/L
Number Analyzed 14 participants 3 participants 46 participants 63 participants
61.33
(0.48 to 1452)
61.6
(19.3 to 95.3)
85.15
(.014 to 3520)
78.7
(0.14 to 3520)
[1]
Measure Description: Prostatic Specific Antigen (PSA) is a test to assess prostate cancer and the normal values are 4.0 ng/mL and lower.
Hemoglobin   [1] 
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 14 participants 3 participants 46 participants 63 participants
12.85
(8.5 to 14.5)
12.1
(12.0 to 13.2)
11.9
(7.4 to 14.8)
12.0
(7.4 to 14.8)
[1]
Measure Description: Hemoglobin is a protein in the blood that carries oxygen and the normal range for men is 13.5 to 17.5 g/dL.
1.Primary Outcome
Title Recommended Phase 2 Dose (RP2D)
Hide Description The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide).
Time Frame 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: mg
25
2.Primary Outcome
Title Count of Participants With Dose-Limiting Toxicities (DLT)
Hide Description DLT is defined as a ≥grade 3 non-hematological toxicity related to lenalidomide.
Time Frame First 28 days of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 63
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Primary Outcome
Title Median Time to Progression (TTP)
Hide Description TTP is evaluated from the on-study date until the date of progression or last follow-up after progression.
Time Frame median time of potential follow-up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m^2 intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 63
Median (95% Confidence Interval)
Unit of Measure: Months
18.2
(15.2 to 26.1)
4.Secondary Outcome
Title Median Overall Survival of Patients Studied
Hide Description OS is evaluated from the on-study date until the date of death or last follow-up.
Time Frame median time of potential follow‐up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 63
Median (95% Confidence Interval)
Unit of Measure: Months
24.6
(21.7 to 31.2)
5.Secondary Outcome
Title Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration
Hide Description The definition of an increase is any increase (any number greater than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient’s percent CAEC among total peripheral blood mononuclear cells at baseline to each patient’s percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. The definition of a decrease is any decrease (any number less than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient’s percent CAEC among total peripheral blood mononuclear cells at baseline to each patient’s percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1.
Time Frame After drug administration, an average of 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 63
Measure Type: Count of Participants
Unit of Measure: Participants
Increase in CAEC after 3 months
30
  47.6%
decrease in CAEC after 3 months
20
  31.7%
6.Secondary Outcome
Title Changes in the Molecular Markers of Angiogenesis (i.e Serum VEGF) Before and After Administration of Docetaxel, Prednisone,Lenalidomide and Bevacizumab
Hide Description Serum and urine samples were collected before and after administration of Docetaxel, Prednisone, Lenalidomide and Bevacizumab to measure VEGF levels.
Time Frame median time of potential follow‐up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not done because the blood samples collected were insufficient for measuring plasma VEGF.
Arm/Group Title Single Arm - 4 Drug Combination
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21

Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells
Hide Description Expression of PD-1 on CD8 + T cells was evaluated by flow cytometry. High and low expression are based on the median values. Patients with a low expression of PD-1 proteins had better survival than those with a high expression.
Time Frame median time of potential follow‐up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 9 3 37
Median (95% Confidence Interval)
Unit of Measure: Months
Low expression
21.4 [1] 
(14.2 to NA)
17.8 [1] 
(NA to NA)
28.9
(13.1 to 43.3)
High expression
22.4 [1] 
(18.1 to NA)
26.1 [1] 
(NA to NA)
14.8
(10.1 to 18.2)
[1]
Not available based on small numbers.
8.Secondary Outcome
Title Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells
Hide Description Expression of TIM-3 on CD8 + T cells was evaluated by flow cytometry.
Time Frame 46.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Lenalidomide 20 mg Lenalidomide 25 mg Lenalidomide
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 1 1 16
Median (95% Confidence Interval)
Unit of Measure: Months
Low expression
23.6 [1] 
(NA to NA)
NA [1] 
(NA to NA)
20.2
(13.1 to 32.0)
High expression
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
12.7
(6.7 to 27.6)
[1]
Not available based on small numbers.
9.Secondary Outcome
Title Count of Participants With a Radiologic Response
Hide Description Radiologic response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame median time of potential follow‐up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Lenalidomide 20 mg Lenalidomide 25 mg Lenalidomide
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 4 2 23
Measure Type: Count of Participants
Unit of Measure: Participants
Confirmed radiologic PR
3
  75.0%
2
 100.0%
20
  87.0%
Complete Response
0
   0.0%
2
 100.0%
0
   0.0%
Stable Disease
1
  25.0%
0
   0.0%
3
  13.0%
10.Secondary Outcome
Title Count of Participants With Prostatic Antigen-Specific (PSA) Declines
Hide Description PSA decline is defined as a ≥50% decline in measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as ≥10 mm with computed tomography, or ≥10 mm with calipers by clinical exam.
Time Frame median time of potential follow‐up of 47.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Lenalidomide 20 mg Lenalidomide 25 mg Lenalidomide
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 13 3 45
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with PSA>30%
13
 100.0%
3
 100.0%
41
  91.1%
Participants with PSA>50%
12
  92.3%
3
 100.0%
40
  88.9%
Participants with PSA>90%
5
  38.5%
1
  33.3%
27
  60.0%
Not Evaluable
1
   7.7%
0
   0.0%
1
   2.2%
11.Secondary Outcome
Title Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 93 months and 22 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Hide Arm/Group Description:

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

Overall Number of Participants Analyzed 14 3 46
Measure Type: Count of Participants
Unit of Measure: Participants
14
 100.0%
3
 100.0%
46
 100.0%
Time Frame Date treatment consent signed to date off study, approximately 93 months and 22 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Hide Arm/Group Description

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone.

Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days

Lenalidomide: Once daily days 1-14 of every 21 days

Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)

Prednisone: 10 mg orally every day

All-Cause Mortality
15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/14 (7.14%)      0/3 (0.00%)      2/46 (4.35%)    
Show Serious Adverse Events Hide Serious Adverse Events
15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/14 (92.86%)      3/3 (100.00%)      45/46 (97.83%)    
Blood and lymphatic system disorders       
Anemia  1  2/14 (14.29%)  2 0/3 (0.00%)  0 4/46 (8.70%)  11
Febrile neutropenia  1  2/14 (14.29%)  3 0/3 (0.00%)  0 8/46 (17.39%)  10
Cardiac disorders       
Heart failure  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Ventricular arrhythmia  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Paroxysmal atrial tachycardia  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Atrial fibrillation  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Chest pain - cardiac  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Myocardial infarction  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Sinus bradycardia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Tricuspid valve disease  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastrointestinal disorders       
Small intestinal perforation  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Nausea  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Rectal fistula  1  0/14 (0.00%)  0 1/3 (33.33%)  1 2/46 (4.35%)  2
Vomiting  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Colitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Colonic perforation  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Diarrhea  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Duodenal ulcer  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Gastric hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastric ulcer  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Gastrointestinal disorders - Other, Diverticulitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastrointestinal pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ileus  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Lower gastrointestinal hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Upper gastrointestinal hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
General disorders       
Death NOS  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Fever  1  0/14 (0.00%)  0 1/3 (33.33%)  2 1/46 (2.17%)  1
Fatigue  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Hepatobiliary disorders       
Cholecystitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations       
Infections and infestations - Other, specify  1 [1]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Lung infection  1  1/14 (7.14%)  1 0/3 (0.00%)  0 7/46 (15.22%)  8
Anorectal infection  1  0/14 (0.00%)  0 1/3 (33.33%)  2 0/46 (0.00%)  0
Infections and infestations - Other, specify  1 [2]  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Enterocolitis infectious  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Bacteremia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infusion related reaction  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Peritoneal infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Scrotal infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Sepsis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Upper respiratory infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Urinary tract infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Injury, poisoning and procedural complications       
Fracture  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Wound dehiscence  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Investigations       
Blood bilirubin increased  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Neutrophil count decreased  1  3/14 (21.43%)  4 3/3 (100.00%)  4 22/46 (47.83%)  43
Platelet count decreased  1  2/14 (14.29%)  4 0/3 (0.00%)  0 3/46 (6.52%)  3
CPK increased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Creatinine increased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Electrocardiogram QT corrected interval prolonged  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Weight loss  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Metabolism and nutrition disorders       
Dehydration  1  1/14 (7.14%)  1 2/3 (66.67%)  3 9/46 (19.57%)  10
Hypoalbuminemia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Hypokalemia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Hyponatremia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Hypophosphatemia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Musculoskeletal and connective tissue disorders       
Myalgia  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Back pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Chest wall pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Myositis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Non-cardiac chest pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Osteonecrosis of jaw  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1 [3]  11/14 (78.57%)  11 3/3 (100.00%)  3 36/46 (78.26%)  36
Nervous system disorders       
Syncope  1  2/14 (14.29%)  2 0/3 (0.00%)  0 3/46 (6.52%)  3
Transient ischemic attacks  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Hypersomnia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Peripheral sensory neuropathy  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Presyncope  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Psychiatric disorders       
Confusion  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Delirium  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Depression  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders       
Acute kidney injury  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Hematuria  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  5
Renal and urinary disorders - Other, urethral stricture  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Urinary retention  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Urinary tract obstruction  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  3
Hypoxia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Productive cough  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Wheezing  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders       
Palmar-plantar erythrodysesthesia syndrome  1  1/14 (7.14%)  3 0/3 (0.00%)  0 0/46 (0.00%)  0
Skin ulceration  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Vascular disorders       
Hypotension  1  1/14 (7.14%)  1 1/3 (33.33%)  1 2/46 (4.35%)  3
Thromboembolic event  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Colon
[2]
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Blood
[3]
Progressive disease
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
15 mg Dose Lenalidomide 20 mg Dose Lenalidomide 25 mg Dose Lenalidomide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      3/3 (100.00%)      46/46 (100.00%)    
Blood and lymphatic system disorders       
Anemia  1  6/14 (42.86%)  49 2/3 (66.67%)  7 24/46 (52.17%)  73
Blood bilirubin increased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Cardiac disorders       
Cardiac disorders - Other, Small pericardial effusion, asymptomatic  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Chest pain - cardiac  1  3/14 (21.43%)  5 0/3 (0.00%)  0 0/46 (0.00%)  0
Palpitations  1  2/14 (14.29%)  2 0/3 (0.00%)  0 0/46 (0.00%)  0
Sinus tachycardia  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Supraventricular tachycardia  1  1/14 (7.14%)  2 0/3 (0.00%)  0 1/46 (2.17%)  1
Atrial fibrillation  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Atrial flutter  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Cardiac disorders - Other, L ventricular hypertrophy  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Conduction disorder  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Sinus bradycardia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Sinus disorder  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Transient ischemic attacks  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Ventricular arrhythmia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ear and labyrinth disorders       
Ear and labyrinth disorders - Other, specify  1 [1]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Ear pain  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Ear and labyrinth disorders - Other, Cerumen impaction b/l-wax removed;  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
External ear inflammation  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Hearing impaired  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Optic nerve disorder  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Otitis externa  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Otitis media  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ear and labyrinth disorders - Other, Cerumen impaction, b/l  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ear and labyrinth disorders - Other, Ear discharge  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ear and labyrinth disorders - Other, Perforated ear drum  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Eye disorders       
Eye disorders - Other, Shrinkage of tear ducts  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Watering eyes  1  2/14 (14.29%)  6 3/3 (100.00%)  3 27/46 (58.70%)  27
Dry eye  1  0/14 (0.00%)  0 1/3 (33.33%)  1 2/46 (4.35%)  3
Blurred vision  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Cataract  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  9
Conjunctivitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Eye disorders - Other, Blepharitis, R. eye  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Eye pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Eye disorders - Other, Erythema b/l eyes  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Eye disorders - Other, Eye cyst  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Eye disorders - Other, Visual changes, intermittent  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastrointestinal disorders       
Abdominal pain  1  3/14 (21.43%)  3 2/3 (66.67%)  5 14/46 (30.43%)  21
Colonic hemorrhage  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Constipation  1  4/14 (28.57%)  5 1/3 (33.33%)  1 19/46 (41.30%)  27
Dental caries  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  3
Diarrhea  1  7/14 (50.00%)  11 3/3 (100.00%)  8 31/46 (67.39%)  79
Dyspepsia  1  1/14 (7.14%)  1 1/3 (33.33%)  2 6/46 (13.04%)  7
Fecal incontinence  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastroesophageal reflux disease  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  3
Gastrointestinal disorders - Other, Gastroenteritis  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Gingival pain  1  1/14 (7.14%)  1 1/3 (33.33%)  1 2/46 (4.35%)  2
Mucositis oral  1  6/14 (42.86%)  7 1/3 (33.33%)  2 22/46 (47.83%)  38
Oral pain  1  4/14 (28.57%)  4 0/3 (0.00%)  0 1/46 (2.17%)  1
Periodontal disease  1  2/14 (14.29%)  3 0/3 (0.00%)  0 0/46 (0.00%)  0
Toothache  1  2/14 (14.29%)  2 2/3 (66.67%)  3 9/46 (19.57%)  10
Upper gastrointestinal hemorrhage  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Vomiting  1  2/14 (14.29%)  2 2/3 (66.67%)  5 9/46 (19.57%)  15
Bloating  1  0/14 (0.00%)  0 1/3 (33.33%)  1 1/46 (2.17%)  1
Dry mouth  1  0/14 (0.00%)  0 2/3 (66.67%)  2 8/46 (17.39%)  8
Dysphagia  1  0/14 (0.00%)  0 1/3 (33.33%)  2 0/46 (0.00%)  0
Hemorrhoidal hemorrhage  1  0/14 (0.00%)  0 1/3 (33.33%)  1 2/46 (4.35%)  2
Hemorrhoids  1  0/14 (0.00%)  0 1/3 (33.33%)  1 5/46 (10.87%)  5
Laryngeal inflammation  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Pharyngolaryngeal pain  1  0/14 (0.00%)  0 3/3 (100.00%)  3 0/46 (0.00%)  0
Sore throat  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Stomach pain  1  0/14 (0.00%)  0 1/3 (33.33%)  2 0/46 (0.00%)  0
Abdominal distension  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Anal hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Anal ulcer  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Ascites  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Cheilitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 5/46 (10.87%)  5
Colitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Gastrointestinal disorders - Other, L arytenoid inflammation  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Nausea  1  4/14 (28.57%)  4 2/3 (66.67%)  4 16/46 (34.78%)  22
Oral dysesthesia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Rectal fistula  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Rectal hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 10/46 (21.74%)  13
Rectal pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  6
Gastrointestinal disorders - Other, Loss of crown to dental implant #14  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Gastrointestinal disorders - Other, Cracked tooth  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastrointestinal disorders - Other, Fracture tooth #14  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastrointestinal disorders - Other, Gingival bleeding  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Gastorintestinal disorders - Other, Gum swelling  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Gastrointestinal disorders - Other, Gum swelling, intermittent  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
General disorders       
Edema limbs  1  3/14 (21.43%)  3 3/3 (100.00%)  5 21/46 (45.65%)  29
Fatigue  1  6/14 (42.86%)  12 3/3 (100.00%)  5 29/46 (63.04%)  45
Fever  1  4/14 (28.57%)  5 3/3 (100.00%)  10 12/46 (26.09%)  23
Flu like symptoms  1  1/14 (7.14%)  1 2/3 (66.67%)  2 2/46 (4.35%)  3
Infusion related reaction  1  3/14 (21.43%)  6 1/3 (33.33%)  2 20/46 (43.48%)  57
Infusion site extravasation  1  2/14 (14.29%)  2 0/3 (0.00%)  0 4/46 (8.70%)  5
Pain  1  6/14 (42.86%)  9 3/3 (100.00%)  5 30/46 (65.22%)  59
Pain in extremity  1  5/14 (35.71%)  6 2/3 (66.67%)  3 16/46 (34.78%)  23
Pharyngolaryngeal pain  1  1/14 (7.14%)  2 0/3 (0.00%)  0 0/46 (0.00%)  0
Chills  1  0/14 (0.00%)  0 2/3 (66.67%)  3 0/46 (0.00%)  0
General disorders and administration site conditions - Other, specify  1 [2]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Injection site reaction  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Immune system disorders       
Cytokine release syndrome  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations       
Gum infection  1  4/14 (28.57%)  7 1/3 (33.33%)  1 5/46 (10.87%)  7
Infections and infestations - Other, specify  1 [3]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Sinusitis  1  3/14 (21.43%)  4 2/3 (66.67%)  4 6/46 (13.04%)  7
Skin infection  1  5/14 (35.71%)  5 1/3 (33.33%)  2 16/46 (34.78%)  25
Upper respiratory infection  1  0/14 (0.00%)  0 2/3 (66.67%)  3 21/46 (45.65%)  34
Urinary tract infection  1  2/14 (14.29%)  2 0/3 (0.00%)  0 9/46 (19.57%)  15
Infections and infestations - Other, specify  1 [4]  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Mucosal infection  1  1/14 (7.14%)  1 1/3 (33.33%)  1 0/46 (0.00%)  0
Pharyngitis  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Soft tissue infection  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Tooth infection  1  0/14 (0.00%)  0 1/3 (33.33%)  1 4/46 (8.70%)  8
Abdominal infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Bronchial infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  8
Eye infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Laryngitis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Lip infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Lung infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  7
Nail infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Salivary gland infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Wound infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Infections and infestations - Other, Jaw infection  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Infections and infestations - Other, R jaw infection  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Infections and infestations - Other, Viral  1  1/14 (7.14%)  1 1/3 (33.33%)  1 0/46 (0.00%)  0
Infections and infestations - Other, Specify  1 [5]  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Infections and infestations - Other, Strep throat diagnosed at Kaiser  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Infections and infestations - Other, upper eye lid - chalazion  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Fungal:oral candidiasis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Specify  1 [6]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Oral fungal  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Stool  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Infections and infestations - Other, Specify  1 [7]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Injury, poisoning and procedural complications       
Bruising  1  2/14 (14.29%)  2 1/3 (33.33%)  1 21/46 (45.65%)  21
Fall  1  3/14 (21.43%)  4 0/3 (0.00%)  0 4/46 (8.70%)  5
Fracture  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  6
Injury, poisoning and procedural complications - Other, specify  1 [8]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Investigations       
Alkaline phosphatase increased  1  1/14 (7.14%)  2 0/3 (0.00%)  0 1/46 (2.17%)  2
Creatinine increased  1  1/14 (7.14%)  1 1/3 (33.33%)  1 6/46 (13.04%)  8
Investigations - Other, specify  1 [9]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Lymphocyte count decreased  1  1/14 (7.14%)  3 0/3 (0.00%)  0 0/46 (0.00%)  0
Platelet count decreased  1  6/14 (42.86%)  12 0/3 (0.00%)  0 10/46 (21.74%)  21
Weight loss  1  0/14 (0.00%)  0 1/3 (33.33%)  1 19/46 (41.30%)  39
White blood cell decreased  1  2/14 (14.29%)  4 0/3 (0.00%)  0 1/46 (2.17%)  1
Neutrophil count decreased  1  6/14 (42.86%)  13 3/3 (100.00%)  17 26/46 (56.52%)  68
Alanine aminotransferase increased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  8
Aspartate aminotransferase increased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  8
Metabolism and nutrition disorders       
Anorexia  1  3/14 (21.43%)  4 3/3 (100.00%)  4 23/46 (50.00%)  27
Dehydration  1  2/14 (14.29%)  2 3/3 (100.00%)  4 16/46 (34.78%)  29
Hypercalcemia  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Hyperglycemia  1  2/14 (14.29%)  8 0/3 (0.00%)  0 3/46 (6.52%)  4
Hyperkalemia  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  5
Hypoalbuminemia  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  6
Hypocalcemia  1  2/14 (14.29%)  2 0/3 (0.00%)  0 0/46 (0.00%)  0
Hyponatremia  1  1/14 (7.14%)  2 1/3 (33.33%)  1 3/46 (6.52%)  3
Hypophosphatemia  1  2/14 (14.29%)  4 1/3 (33.33%)  5 10/46 (21.74%)  22
Hypomagnesemia  1  0/14 (0.00%)  0 2/3 (66.67%)  7 30/46 (65.22%)  64
Glucose intolerance  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Hypermagnesemia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Hypokalemia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 7/46 (15.22%)  13
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/14 (7.14%)  1 1/3 (33.33%)  5 2/46 (4.35%)  2
Back pain  1  3/14 (21.43%)  5 1/3 (33.33%)  1 16/46 (34.78%)  24
Bone pain  1  2/14 (14.29%)  2 1/3 (33.33%)  1 9/46 (19.57%)  10
Generalized muscle weakness  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Neck pain  1  2/14 (14.29%)  2 0/3 (0.00%)  0 1/46 (2.17%)  2
Muscle weakness upper limb  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Myalgia  1  3/14 (21.43%)  3 2/3 (66.67%)  3 13/46 (28.26%)  20
Non-cardiac chest pain  1  2/14 (14.29%)  3 1/3 (33.33%)  1 3/46 (6.52%)  4
Osteonecrosis of jaw  1  5/14 (35.71%)  7 3/3 (100.00%)  5 13/46 (28.26%)  19
Arthritis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Flank pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Joint effusion  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Joint range of motion decreased  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Muscle weakness lower limb  1  0/14 (0.00%)  0 0/3 (0.00%)  0 6/46 (13.04%)  9
Muscle weakness trunk  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Musculoskeletal and connective tissue disorder - Other, specify  1 [10]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Musculoskeletal and connective tissue disorders - Other, Specify  1 [11]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Musculoskeletal and connective tissue disorders, Other, R ankle sprain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Nervous system disorders       
Acoustic nerve disorder NOS  1  1/14 (7.14%)  3 0/3 (0.00%)  0 0/46 (0.00%)  0
Dizziness  1  2/14 (14.29%)  2 3/3 (100.00%)  9 15/46 (32.61%)  18
Dysgeusia  1  4/14 (28.57%)  7 2/3 (66.67%)  5 30/46 (65.22%)  33
Headache  1  3/14 (21.43%)  5 3/3 (100.00%)  4 7/46 (15.22%)  7
Hypoglossal nerve disorder  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Nervous system disorders - Other, specify  1 [12]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Peripheral sensory neuropathy  1  6/14 (42.86%)  14 3/3 (100.00%)  5 28/46 (60.87%)  47
Paresthesia  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Tremor  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Vasovagal reaction  1  0/14 (0.00%)  0 1/3 (33.33%)  1 4/46 (8.70%)  4
Intracranial hemorrhage  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Memory impairment  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Nervous system disorders - Other, specify  1 [13]  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Peripheral motor neuropathy  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Syncope  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Psychiatric disorders       
Agitation  1  1/14 (7.14%)  1 1/3 (33.33%)  1 3/46 (6.52%)  3
Confusion  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Depression  1  1/14 (7.14%)  1 1/3 (33.33%)  1 4/46 (8.70%)  6
Insomnia  1  3/14 (21.43%)  3 1/3 (33.33%)  1 10/46 (21.74%)  10
Anxiety  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Hallucinations  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Personality change  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Suicidal ideation  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders - Other, Bleeding at nephrostomy tube site  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders       
Hematuria  1  1/14 (7.14%)  3 0/3 (0.00%)  0 3/46 (6.52%)  3
Proteinuria  1  3/14 (21.43%)  9 0/3 (0.00%)  0 10/46 (21.74%)  24
Urinary incontinence  1  2/14 (14.29%)  3 0/3 (0.00%)  0 5/46 (10.87%)  6
Urinary retention  1  1/14 (7.14%)  3 1/3 (33.33%)  3 4/46 (8.70%)  7
Urinary tract obstruction  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  4
Urinary tract infection  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Renal and urinary disorders - Other, Acute R hydronephrosis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Urinary frequency  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  3
Urinary tract pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders - Other, CR CL < 50  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders - Other, Decreased urinary flow  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders - Other, R hydronephrosis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Renal and urinary disorders - Other, Urinary hesitancy  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Reproductive system and breast disorders       
Scrotal pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis  1  2/14 (14.29%)  2 1/3 (33.33%)  1 11/46 (23.91%)  11
Cough  1  3/14 (21.43%)  4 1/3 (33.33%)  1 15/46 (32.61%)  19
Dyspnea  1  2/14 (14.29%)  3 3/3 (100.00%)  5 21/46 (45.65%)  34
Epistaxis  1  4/14 (28.57%)  5 1/3 (33.33%)  1 27/46 (58.70%)  33
Hoarseness  1  1/14 (7.14%)  2 0/3 (0.00%)  0 9/46 (19.57%)  10
Nasal congestion  1  3/14 (21.43%)  3 0/3 (0.00%)  0 6/46 (13.04%)  7
Pharyngeal mucositis  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Pleural effusion  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Postnasal drip  1  1/14 (7.14%)  1 0/3 (0.00%)  0 3/46 (6.52%)  3
Sore throat  1  2/14 (14.29%)  3 0/3 (0.00%)  0 2/46 (4.35%)  2
Voice alteration  1  1/14 (7.14%)  1 3/3 (100.00%)  3 16/46 (34.78%)  17
Respiratory, thoracic and mediastinal disorders - Other, specify  1 [14]  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Hypoxia  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Pharyngolaryngeal pain  1  0/14 (0.00%)  0 0/3 (0.00%)  0 5/46 (10.87%)  5
Productive cough  1  0/14 (0.00%)  0 0/3 (0.00%)  0 4/46 (8.70%)  4
Respiratory, thoracic and mediastinal disorders - Other, specify  1  0/14 (0.00%)  0 0/3 (0.00%)  0 13/46 (28.26%)  13
Upper respiratory infection  1  0/14 (0.00%)  0 0/3 (0.00%)  0 21/46 (45.65%)  34
Wheezing  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders       
Alopecia  1  2/14 (14.29%)  2 2/3 (66.67%)  2 33/46 (71.74%)  33
Dry skin  1  1/14 (7.14%)  1 1/3 (33.33%)  1 12/46 (26.09%)  15
Nail loss  1  1/14 (7.14%)  3 3/3 (100.00%)  3 10/46 (21.74%)  10
Palmar-plantar erythrodysesthesia syndrome  1  1/14 (7.14%)  4 3/3 (100.00%)  4 7/46 (15.22%)  9
Pruritus  1  3/14 (21.43%)  5 2/3 (66.67%)  2 13/46 (28.26%)  15
Purpura  1  1/14 (7.14%)  1 0/3 (0.00%)  0 5/46 (10.87%)  5
Rash acneiform  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Rash maculo-papular  1  2/14 (14.29%)  4 2/3 (66.67%)  3 12/46 (26.09%)  19
Skin and subcutaneous tissue disorders - Other, specify  1 [15]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Skin hyperpigmentation  1  1/14 (7.14%)  1 2/3 (66.67%)  2 8/46 (17.39%)  10
Skin ulceration  1  1/14 (7.14%)  1 2/3 (66.67%)  2 5/46 (10.87%)  5
Skin and subcutaneous tissue disorders - Other, R hallux valgus  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Skin hypopigmentation  1  0/14 (0.00%)  0 1/3 (33.33%)  1 0/46 (0.00%)  0
Hyperhidrosis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Nail discoloration  1  0/14 (0.00%)  0 0/3 (0.00%)  0 10/46 (21.74%)  10
Nail ridging  1  0/14 (0.00%)  0 0/3 (0.00%)  0 3/46 (6.52%)  3
Pain of skin  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Actinic Keratosis  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin atrophy  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin induration  1  0/14 (0.00%)  0 0/3 (0.00%)  0 2/46 (4.35%)  2
Urticaria  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, angiomas  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, chrondrodermatitis nodularis helicus  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Corn-like lesion R heel  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Depession L temporal area  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Erythema  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Ingrown toenail, medial R big toe  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, L foot halux bunion  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, nail splinter hemorrhages  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, skin breakdown on R hip  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, skin fragility and thinning  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, symptomatic corn on R lateral foot  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Skin and subcutaneous tissue disorders - Other, Bruising and fragility of skin  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, Eschar on L. buttock  1  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, Specify  1 [16]  1/14 (7.14%)  1 0/3 (0.00%)  0 0/46 (0.00%)  0
Vascular disorders       
Hypertension  1  5/14 (35.71%)  6 1/3 (33.33%)  1 18/46 (39.13%)  34
Phlebitis  1  1/14 (7.14%)  1 0/3 (0.00%)  0 1/46 (2.17%)  1
Thromboembolic event  1  1/14 (7.14%)  1 0/3 (0.00%)  0 2/46 (4.35%)  2
Hypotension  1  0/14 (0.00%)  0 1/3 (33.33%)  2 13/46 (28.26%)  23
Flushing  1  0/14 (0.00%)  0 0/3 (0.00%)  0 7/46 (15.22%)  8
Hematoma  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Lymphedema  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  2
Vascular disorders - Other, Conjunctival hemorrhage b/l  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Vascular disorders - Other, L ear bleeding  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
Vascular disorders - Other, Raynaud Syndrome symptoms  1  0/14 (0.00%)  0 0/3 (0.00%)  0 1/46 (2.17%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
R ear pressure d/t dry cerumen impaction which was removed on 1/22/13
[2]
Cold intolerance
[3]
Caseating keratin plug with pus on ear drum in R ear removed
[4]
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Nose
[5]
Infection with normal ANC or Grade 1 or 2 neutrophils:Stomach
[6]
Gastrointestinal-Aeromonas Veronii
[7]
Subgingival, R mandible suggestive of ONJ
[8]
L leg laceration with stitches removed on 9/12/11
[9]
Low serum iron
[10]
Compression fracture
[11]
Muscle cramps/myalgia grade change over baseline
[12]
Intermittent imbalance x 1 yr with worsening this pat month
[13]
Dystonic reaction
[14]
Rhinorrhea
[15]
Acquired perforating dermatosis elbows
[16]
Poor wound healing at extraction site of tooth #31
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Ravi Madan
Organization: National Cancer Institute
Phone: 301-480-7168
EMail: rm480i@nih.gov
Layout table for additonal information
Responsible Party: Ravi A. Madan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00942578     History of Changes
Other Study ID Numbers: 090195
09-C-0195
First Submitted: July 18, 2009
First Posted: July 21, 2009
Results First Submitted: July 25, 2018
Results First Posted: October 11, 2018
Last Update Posted: October 11, 2018