Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT00892177

Recruitment Status : Completed

First Posted : May 4, 2009

Results First Posted : June 27, 2017

Last Update Posted : October 21, 2019

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Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Alliance for Clinical Trials in Oncology

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Glioblastoma Multiforme
Interventions	Biological: bevacizumab Drug: dasatinib Other: placebo
Enrollment	144

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Phase I: Dose Level 0	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase I: Dose Level 3	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description	Patients receive 5 mg/kg bevacizuma...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description	Patients receive 5 mg/kg bevacizumab IV over 90 minutes on Day 1 and 50 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 50 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 70 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 100 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Period Title: Phase I: Dose Level 0
Started	3	0	0	0	0	0
Completed	3	0	0	0	0	0
Not Completed	0	0	0	0	0	0
Period Title: Phase I: Dose Level 1
Started	0	4	0	0	0	0
Completed	0	4	0	0	0	0
Not Completed	0	0	0	0	0	0
Period Title: Phase I: Dose Level 2
Started	0	0	3	0	0	0
Completed	0	0	3	0	0	0
Not Completed	0	0	0	0	0	0
Period Title: Phase I: Dose Level 3
Started	0	0	0	6	0	0
Completed	0	0	0	6	0	0
Not Completed	0	0	0	0	0	0
Period Title: Phase II
Started	0	0	0	0	88	40
Completed	0	0	0	0	83	38
Not Completed	0	0	0	0	5	2
Reason Not Completed
Ineligible	0	0	0	0	1	1
Withdrawal by Subject	0	0	0	0	4	1

Baseline Characteristics

Arm/Group Title		Phase I	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)	Total
Arm/Group Description		Patients receive (either: 5 or 10 m...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Total of all reporting groups
Arm/Group Description		Patients receive (either: 5 or 10 mg/kg) bevacizumab IV over 90 minutes on Day 1 and oral dasatinib (either: 50, 70, or 100 mg) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Number of Baseline Participants		16	83	38	137
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	16 participants	83 participants	38 participants	137 participants
		46.5 (28 to 68)	58 (29 to 79)	56.5 (18 to 71)	57 (18 to 79)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	16 participants	83 participants	38 participants	137 participants
	Female	3 18.8%	28 33.7%	16 42.1%	47 34.3%
	Male	13 81.3%	55 66.3%	22 57.9%	90 65.7%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	16 participants	83 participants	38 participants	137 participants
United States		16 100.0%	83 100.0%	38 100.0%	137 100.0%

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Bevacizumab (Phase I)
Description	The Maximum Tolerated Dose (MTD) will be based on the assessment of do...
Description	The Maximum Tolerated Dose (MTD) will be based on the assessment of dose-limiting toxicities (DLT) during the first 4 weeks of treatment only (i.e., following the first 2 treatment cycles), and will be defined as the dose at which fewer than one-third of patients experience a DLT to study treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with the next higher dose having at least 2 out of 3 or 2 out of 6 patients encountering DLT.> Three patients will be treated at each dose level, and can be enrolled simultaneously. If one DLT is encountered, an additional 3 patients will be added to that dose level. If at any point two DLTs are encountered within a given dose level, then the MTD has been exceeded and if only three patients have been treated at the next lower dose three more patients are treated at the next lower dose. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Adverse event information is available for 4 patients on study 1 dose level 1 (with 1 being a MTD replacement due to disease progression prior to completing cycles 1 and 2).


Arm/Group Title	Phase I : Dose Level 0	Phase I : Dose Level 1	Phase I : Dose Level 2	Phase I : Dose Level 3 Cohort 1	Phase I: Dose Level 3 Cohort 2
Arm/Group Description:	Patients receive 5 mg/kg bevacizuma...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 5 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 50 mg twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 50 mg twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 70 mg twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	3	4	3	3	3
Measure Type: Number Unit of Measure: participants who developed DLTs
	0	0	0	0	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase I : Dose Level 0, Phase I : Dose Level 1, Phase I : Dose Level 2, Phase I : Dose Level 3 Cohort 1, Phase I: Dose Level 3 Cohort 2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Maximum Tolerated Dose (mg)
	Estimated Value	100
	Estimation Comments	[Not Specified]

2.Primary Outcome


Title	Progression-free Survival at 6 Months (PFS6) (Phase II)
Description	The primary endpoint is the proportion of patients alive and progressi...
Description	The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation (PFS6). All eligible consented patients that received treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. PFS6 is defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause. 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 PFS6 will be estimated as the number of evaluable patients progression free and still alive at 6 months divided by the total number of evaluable patients. The confidence interval will be calculated according to the Clopper-Pearson Method.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All patients that received treatment and were eligible for assessment were included in this analysis.


Arm/Group Title	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	83	38
Measure Type: Number Number (90% Confidence Interval) Unit of Measure: proportion of participants
	0.29 (0.19 to 0.39)	0.18 (0.08 to 0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase II: Arm A (Bevacizumab + Dasatinib), Phase II: Arm B (Bevacizumab + Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.22
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95% -0.052 to 0.262
	Estimation Comments	Difference in proportion

3.Secondary Outcome


Title	Number of Participants With Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 (Phase II)
Description	Adverse events were collected systematically at the end of each cycle ...
Description	Adverse events were collected systematically at the end of each cycle and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. Events are scored as: 1="Mild symptoms", 2= "Moderate", 3="Severe", 4="Life-threatening", and 5="Death". The number of patients reporting a grade 3 or higher event regardless of attribution are summarized here. A complete list of all adverse events reported during treatment can be found in the Adverse Events Section.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All Phase II patients treated and evaluated for adverse events are included in this Phase II endpoint analysis.


Arm/Group Title	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	83	38
Measure Type: Number Unit of Measure: participants
Grade 3 Adverse Event	42	23
Grade 4 Adverse Event	8	2
Grade 5 Adverse Event	5	3

4.Secondary Outcome


Title	Overall Survival (Phase II)
Description	Survival time is defined to be the length of time from start of study ...
Description	Survival time is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both arms of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible Phase II patients are included in this Phase II endpoint analysis.


Arm/Group Title	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	83	38
Median (95% Confidence Interval) Unit of Measure: months
	7.3 (6.2 to 8.7)	7.9 (6.6 to 11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase II: Arm A (Bevacizumab + Dasatinib), Phase II: Arm B (Bevacizumab + Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7
	Comments	[Not Specified]
	Method	Kaplan Meier
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.61 to 1.4
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Time-to-disease Progression (Phase II)
Description	Time-to-disease progression is defined as the time from start of study...
Description	Time-to-disease progression is defined as the time from start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death unless there is documented evidence that no progression occurred before death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy or date last known to be alive, whichever is later. Patients who are still alive and have not progressed will be censored for progression at the time of the last tumor assessment. Patients who experience major treatment violations will be censored for progression on the date the treatment violation occurred. The time-to-progression distribution will be estimated using the Kaplan-Meier method.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible Phase II patients are included in this Phase II endpoint analysis.


Arm/Group Title	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	83	38
Median (95% Confidence Interval) Unit of Measure: months
	3.3 (2.79 to 4.6)	3.5 (2.83 to 4.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase II: Arm A (Bevacizumab + Dasatinib), Phase II: Arm B (Bevacizumab + Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.52
	Comments	[Not Specified]
	Method	Kaplan Meier
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95% 0.76 to 1.7
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Patient-reported QOL, as Measure by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) (Phase II)
Description	FACT-Br questionnaires were used to assess QOL at every other cycle of...
Description	FACT-Br questionnaires were used to assess QOL at every other cycle of treatment (prior to cycles 3, 5, 7, etc.). FACT-Br includes 50 questions used to assess patients' self-assessment in 4 broad categories: Physical, Social/Family, Emotional, and Function Well-being. Scores range from 0="Not at all", 1="A little bit", 2="Somewhat", 3="Quite a bit", 4="Very Much". Higher scores can be interpreted as having higher quality of life. The scores for all 50 questions were summed to give a total score per patient per cycle. Therefore the possible range is from 0 to 200. Below is the reported mean and standard deviation for patients at baseline and during cycles 2, 4, 6, 8, and 10.
Time Frame	Baseline to cycle 10 (20 weeks).

Outcome Measure Data

Analysis Population Description

All Phase II patients that began treatment and submitted at least one FACT-Br questionnaire were included in this analysis.


Arm/Group Title		Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:		Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed		77	34
Mean (Standard Deviation) Unit of Measure: units on a scale
Cycle 0	Number Analyzed	77 participants	34 participants
Cycle 0		139.5 (26.2)	138.3 (22.4)
Cycle 2	Number Analyzed	55 participants	23 participants
Cycle 2		131.2 (27.9)	133.5 (23.5)
Cycle 4	Number Analyzed	29 participants	16 participants
Cycle 4		137.6 (30.1)	137.4 (23.1)
Cycle 6	Number Analyzed	30 participants	13 participants
Cycle 6		140.1 (29.0)	137.7 (25.7)
Cycle 8	Number Analyzed	17 participants	9 participants
Cycle 8		142.3 (30.2)	142.8 (31.1)
Cycle10	Number Analyzed	12 participants	5 participants
Cycle10		142.1 (34.9)	149.3 (34.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase II: Arm A (Bevacizumab + Dasatinib), Phase II: Arm B (Bevacizumab + Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.96
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.223
	Estimation Comments	The estimate is the net difference between Arm A and Arm B total score using information from all cycles. A negative value means that Arm A has a lower quality of life and a positive value means Arm A has a higher reported quality of life.

7.Secondary Outcome


Title	Objective Response (Phase II)
Description	Objective response to treatment will be determined by the results of n...
Description	Objective response to treatment will be determined by the results of neurological exam and the MRI and/or CT measurement of the tumor at each evaluation as is used for all NCCTG neuro-oncology trials. The percentage of patients in each response category will be summarized, 95% confidence intervals calculated, and rates between the 2 arms will be compared using a Fisher's Exact test. For bi-dimensionally measurable disease, CR: total disappearance of all tumor and that patients be on no corticosteroids or on only adrenal replacement maintenance; PR: ≥ 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions, and stable or decreasing steroid dosing; PD: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions; REGR: unequivocal reduction in extent of contrast-enhancement, or a decrease in mass effect, no new lesions (for evaluable disease); SD: failure to qualify for CR, PR,REGR or PD.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible Phase II patients are included in this Phase II endpoint analysis.


Arm/Group Title	Phase II: Arm A (Bevacizumab + Dasatinib)	Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description:	Patients receive 10 mg/kg bevacizum...	Patients receive 10 mg/kg bevacizum...
Arm/Group Description:	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	83	38
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
CR	2.4 (0.5 to 7.4)	2.6 (0 to 11.8)
PR	2.4 (0.5 to 7.4)	5.3 (1.1 to 15.3)
REGR	10.8 (6.3 to 17.9)	18.4 (10.1 to 30.9)
SD	57.8 (48.8 to 66.4)	57.9 (44.6 to 70.1)
PD	12.0 (7.2 to 19.3)	5.3 (1.1 to 15.3)
Missing/Unknown	14.5 (9.1 to 22.0)	10.5 (4.4 to 21.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase II: Arm A (Bevacizumab + Dasatinib), Phase II: Arm B (Bevacizumab + Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6325
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events are assessed 21 days prior to registration, prior to each new cycle, and at time of progression, withdrawal or removal from the study up to 3 years from registration.
Adverse Event Reporting Description	CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for expedited adverse event reporting only, beginning July 1, 2011.

Arm/Group Title	Phase I: Dose Level 0		Phase I: Dose Level 1		Phase I: Dose Level 2		Phase I: Dose Level 3		Phase II: Arm A (Bevacizumab + Dasatinib)		Phase II: Arm B (Bevacizumab + Placebo)
Arm/Group Description	Patients receive 5 mg/kg bevacizuma...		Patients receive 10 mg/kg bevacizum...		Patients receive 10 mg/kg bevacizum...		Patients receive 10 mg/kg bevacizum...		Patients receive 10 mg/kg bevacizum...		Patients receive 10 mg/kg bevacizum...
Arm/Group Description	Patients receive 5 mg/kg bevacizumab IV over 90 minutes on Day 1 and 50 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 50 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 70 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and 100 mg oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral dasatinib 100 mg (2 tablets) twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.		Patients receive 10 mg/kg bevacizumab IV over 90 minutes on Day 1 and oral placebo twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Phase I: Dose Level 0		Phase I: Dose Level 1		Phase I: Dose Level 2		Phase I: Dose Level 3		Phase II: Arm A (Bevacizumab + Dasatinib)		Phase II: Arm B (Bevacizumab + Placebo)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	Phase I: Dose Level 0		Phase I: Dose Level 1		Phase I: Dose Level 2		Phase I: Dose Level 3		Phase II: Arm A (Bevacizumab + Dasatinib)		Phase II: Arm B (Bevacizumab + Placebo)
	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	2/3 (66.67%)		1/4 (25.00%)		2/3 (66.67%)		1/6 (16.67%)		32/84 (38.10%)		18/39 (46.15%)
Blood and lymphatic system disorders
Hemoglobin decreased ^† 1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Leukocytosis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Cardiac disorders
Cardiac disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Myocardial ischemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Sinus arrhythmia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Sinus tachycardia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Eye disorders
Eye disorders - Other, specify ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Optic nerve disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Gastrointestinal disorders
Abdominal pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Anal hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Colitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Colonic perforation ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Diarrhea ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	3/84 (3.57%)	3	0/39 (0.00%)	0
Ear, nose and throat examination abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Ileal obstruction ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Jejunal perforation ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Nausea ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	1
Rectal hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Retroperitoneal hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Vomiting ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
General disorders
Chest pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Death ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Disease progression ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Edema limbs ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Fatigue ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/6 (0.00%)	0	3/84 (3.57%)	3	3/39 (7.69%)	4
Fever ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	3/39 (7.69%)	3
Gait abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Sudden death ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/6 (0.00%)	0	0/84 (0.00%)	0	0/39 (0.00%)	0
Infections and infestations
Bladder infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Catheter related infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Lung infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Pneumonia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	3	1/39 (2.56%)	1
Sepsis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	2/39 (5.13%)	2
Soft tissue infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Urinary tract infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Wound infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Injury, poisoning and procedural complications
Fracture ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	2/39 (5.13%)	21
Intraoperative complications ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Wound dehiscence ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Investigations
Bilirubin increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Creatinine increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Laboratory test abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Neutrophil count decreased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Platelet count decreased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Weight loss ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Metabolism and nutrition disorders
Anorexia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	2/84 (2.38%)	2	0/39 (0.00%)	0
Blood glucose increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Dehydration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	2/84 (2.38%)	2	1/39 (2.56%)	1
Serum phosphate decreased ^† 1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Generalized muscle weakness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Muscle weakness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	5	0/39 (0.00%)	0
Muscle weakness left-sided ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Muscle weakness lower limb ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	2
Muscle weakness right-sided ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Musculoskeletal disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Pain in extremity ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Nervous system disorders
Ataxia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	1/39 (2.56%)	1
Cognitive disturbance ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Depressed level of consciousness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	2
Dysphasia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Extrapyramidal disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Headache ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Ischemia cerebrovascular ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Memory impairment ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Seizure ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	4/39 (10.26%)	4
Somnolence ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Syncope ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Psychiatric disorders
Confusion ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	2/39 (5.13%)	4
Renal and urinary disorders
Bladder hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Cystitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Atelectasis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Dyspnea ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Epistaxis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Hypoxia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Pleural effusion ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Respiratory disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	1
Skin and subcutaneous tissue disorders
Rash desquamating ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Vascular disorders
Hematoma ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Hypertension ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Hypotension ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Thrombosis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	3/39 (7.69%)	4
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 9
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Phase I: Dose Level 0		Phase I: Dose Level 1		Phase I: Dose Level 2		Phase I: Dose Level 3		Phase II: Arm A (Bevacizumab + Dasatinib)		Phase II: Arm B (Bevacizumab + Placebo)
	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	3/3 (100.00%)		4/4 (100.00%)		3/3 (100.00%)		6/6 (100.00%)		83/84 (98.81%)		39/39 (100.00%)
Blood and lymphatic system disorders
Hemoglobin decreased ^† 1	3/3 (100.00%)	28	2/4 (50.00%)	24	2/3 (66.67%)	22	5/6 (83.33%)	20	67/84 (79.76%)	432	14/39 (35.90%)	38
Cardiac disorders
Atrial fibrillation ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Sinus tachycardia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Ear and labyrinth disorders
Hearing test abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Tinnitus ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Endocrine disorders
Cushingoid ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Eye disorders
Cataract ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Eye disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Gastrointestinal disorders
Abdominal distension ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Abdominal pain ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	2	0/3 (0.00%)	0	1/6 (16.67%)	1	10/84 (11.90%)	17	7/39 (17.95%)	14
Anal pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Constipation ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	6/84 (7.14%)	8	0/39 (0.00%)	0
Diarrhea ^† 1	1/3 (33.33%)	6	1/4 (25.00%)	6	1/3 (33.33%)	2	3/6 (50.00%)	13	50/84 (59.52%)	186	12/39 (30.77%)	51
Dyspepsia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	3	3/84 (3.57%)	4	0/39 (0.00%)	0
Dysphagia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	9
Ear, nose and throat examination abnormal ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	6	1/3 (33.33%)	2	0/6 (0.00%)	0	11/84 (13.10%)	17	2/39 (5.13%)	3
Gastrointestinal pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	3	0/39 (0.00%)	0
Hemorrhoids ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Ileus ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Mucositis oral ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/6 (0.00%)	0	8/84 (9.52%)	13	4/39 (10.26%)	9
Nausea ^† 1	1/3 (33.33%)	1	1/4 (25.00%)	2	1/3 (33.33%)	1	2/6 (33.33%)	3	31/84 (36.90%)	82	11/39 (28.21%)	37
Tooth disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Upper gastrointestinal hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Vomiting ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	17/84 (20.24%)	35	4/39 (10.26%)	6
General disorders
Edema limbs ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	1/39 (2.56%)	1
Facial pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Fatigue ^† 1	3/3 (100.00%)	50	4/4 (100.00%)	37	3/3 (100.00%)	29	6/6 (100.00%)	57	73/84 (86.90%)	478	35/39 (89.74%)	241
Fever ^† 1	1/3 (33.33%)	1	1/4 (25.00%)	1	0/3 (0.00%)	0	1/6 (16.67%)	1	16/84 (19.05%)	18	2/39 (5.13%)	2
Flu-like symptoms ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	1/39 (2.56%)	1
Gait abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Infections and infestations
Abdominal infection ^† 1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Appendicitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Bladder infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	1/84 (1.19%)	1	0/39 (0.00%)	0
Bone infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Bronchitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	3	0/39 (0.00%)	0
Encephalitis infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Gingival infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	1/39 (2.56%)	1
Joint infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Mucosal infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Opportunistic infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Otitis externa ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Pneumonia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Sinusitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Skin infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	1
Tooth infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Upper respiratory infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Urinary tract infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	6	0/39 (0.00%)	0
Wound infection ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Injury, poisoning and procedural complications
Fracture ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	4	1/39 (2.56%)	1
Wound dehiscence ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	1/6 (16.67%)	1	1/84 (1.19%)	1	0/39 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	5/84 (5.95%)	10	2/39 (5.13%)	2
Aspartate aminotransferase increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	11	1/39 (2.56%)	1
Blood gonadotrophin abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Cardiac troponin I increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Creatinine increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	4	0/39 (0.00%)	0
Electrocardiogram QTc interval prolonged ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Investigations - Other, specify ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Leukocyte count decreased ^† 1	2/3 (66.67%)	14	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	29/84 (34.52%)	97	6/39 (15.38%)	13
Lymphocyte count decreased ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	2/6 (33.33%)	3	13/84 (15.48%)	35	7/39 (17.95%)	19
Lymphocyte count increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Neutrophil count decreased ^† 1	2/3 (66.67%)	23	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	14/84 (16.67%)	51	1/39 (2.56%)	3
Platelet count decreased ^† 1	2/3 (66.67%)	16	1/4 (25.00%)	1	2/3 (66.67%)	4	3/6 (50.00%)	5	47/84 (55.95%)	180	13/39 (33.33%)	29
Weight gain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	6	0/39 (0.00%)	0
Weight loss ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	1/6 (16.67%)	1	27/84 (32.14%)	182	11/39 (28.21%)	105
Metabolism and nutrition disorders
Anorexia ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	30	0/3 (0.00%)	0	0/6 (0.00%)	0	34/84 (40.48%)	114	13/39 (33.33%)	70
Blood glucose increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	8	1/39 (2.56%)	1
Dehydration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Hypermagnesemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Hypoalbuminemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Hypocalcemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	1/39 (2.56%)	1
Hypokalemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	1/39 (2.56%)	1
Hypophosphatemia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	1
Serum albumin decreased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	8/84 (9.52%)	12	0/39 (0.00%)	0
Serum calcium decreased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	8/84 (9.52%)	14	0/39 (0.00%)	0
Serum phosphate decreased ^† 1	1/3 (33.33%)	3	2/4 (50.00%)	3	0/3 (0.00%)	0	0/6 (0.00%)	0	21/84 (25.00%)	33	3/39 (7.69%)	3
Serum potassium decreased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	1
Serum potassium increased ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Serum sodium decreased ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	6/84 (7.14%)	8	2/39 (5.13%)	4
Generalized muscle weakness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Joint pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	2
Muscle weakness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	5/84 (5.95%)	48	2/39 (5.13%)	7
Muscle weakness left-sided ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	5
Muscle weakness lower limb ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	6	3/39 (7.69%)	4
Muscle weakness right-sided ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	1
Muscle weakness upper limb ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	2
Myalgia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Neck pain ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Pain in extremity ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	2/39 (5.13%)	19
Nervous system disorders
Acoustic nerve disorder NOS ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	2
Ataxia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Central nervous system necrosis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Cognitive disturbance ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	6	1/39 (2.56%)	2
Depressed level of consciousness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Dizziness ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	3/39 (7.69%)	3
Dysarthria ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Dysgeusia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Dysphasia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	3	0/39 (0.00%)	0
Headache ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	7/84 (8.33%)	12	4/39 (10.26%)	4
Memory impairment ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	2
Mini mental status examination abnormal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Nervous system disorders - Other, specify ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Neurological disorder NOS ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	3
Peripheral motor neuropathy ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Peripheral sensory neuropathy ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	3	0/39 (0.00%)	0
Seizure ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	5/84 (5.95%)	7	2/39 (5.13%)	2
Speech disorder ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	3	5/39 (12.82%)	22
Taste alteration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	5	0/39 (0.00%)	0
Psychiatric disorders
Agitation ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	5	1/39 (2.56%)	3
Anxiety ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	5/84 (5.95%)	8	0/39 (0.00%)	0
Confusion ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	7	4/39 (10.26%)	7
Depression ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	5/84 (5.95%)	14	3/39 (7.69%)	14
Insomnia ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	5/84 (5.95%)	5	2/39 (5.13%)	2
Personality change ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	10	0/39 (0.00%)	0
Renal and urinary disorders
Protein urine positive ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	2/84 (2.38%)	15	1/39 (2.56%)	5
Renal failure ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Urinary incontinence ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	2	0/39 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Apnea ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	2	0/39 (0.00%)	0
Aspiration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Atelectasis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	3	0/39 (0.00%)	0
Cough ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	3	1/39 (2.56%)	2
Dyspnea ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	3/84 (3.57%)	5	0/39 (0.00%)	0
Hemorrhage nasal ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Pharyngeal examination abnormal ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Pharyngeal mucositis ^† 1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	2/39 (5.13%)	7
Pleural effusion ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	6/84 (7.14%)	14	0/39 (0.00%)	0
Pneumonitis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	1/84 (1.19%)	1	0/39 (0.00%)	0
Voice alteration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Skin and subcutaneous tissue disorders
Decubitus ulcer ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	10	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Dry skin ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	0/84 (0.00%)	0	1/39 (2.56%)	1
Pruritus ^† 1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Rash acneiform ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	2/84 (2.38%)	4	0/39 (0.00%)	0
Rash desquamating ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	16	0/84 (0.00%)	0	0/39 (0.00%)	0
Skin ulceration ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	0/39 (0.00%)	0
Urticaria ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	1/84 (1.19%)	1	1/39 (2.56%)	2
Vascular disorders
Hemorrhage ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/6 (16.67%)	1	0/84 (0.00%)	0	0/39 (0.00%)	0
Hypertension ^† 1	0/3 (0.00%)	0	2/4 (50.00%)	11	2/3 (66.67%)	4	4/6 (66.67%)	14	28/84 (33.33%)	131	18/39 (46.15%)	92
Thrombosis ^† 1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/6 (0.00%)	0	4/84 (4.76%)	6	2/39 (5.13%)	2
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 9

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

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Name/Title:	Evanthia Galanis, M.D.
Organization:	Mayo Clinic
Phone:	(507) 284-7733
EMail:	galanis.evanthia@mayo.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Galanis E, Anderson SK, Twohy EL, Carrero XW, Dixon JG, Tran DD, Jeyapalan SA, Anderson DM, Kaufmann TJ, Feathers RW, Giannini C, Buckner JC, Anastasiadis PZ, Schiff D. A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872. Cancer. 2019 Nov 1;125(21):3790-3800. doi: 10.1002/cncr.32340. Epub 2019 Jul 10.

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Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT00892177
Other Study ID Numbers:	NCCTG-N0872 NCI-2011-01921 ( Registry Identifier: CTRP (Clinical Trials Reporting System) ) CDR0000641746 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted:	May 1, 2009
First Posted:	May 4, 2009
Results First Submitted:	March 13, 2017
Results First Posted:	June 27, 2017
Last Update Posted:	October 21, 2019

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