Trial Outcomes & Findings for Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer (NCT NCT01727089)

Last Updated: 2018-08-28

Results Overview

Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

The duration of time from start of treatment to time of progression or death, assessed at 24 weeks

Results posted on

2018-08-28

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Bevacizumab) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Study STARTED	29	30
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Bevacizumab) n=29 Participants Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 Participants Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies	Total n=59 Participants Total of all reporting groups
Age, Continuous	58 years n=93 Participants	65 years n=4 Participants	60 years n=27 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	6 Participants n=4 Participants	15 Participants n=27 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	24 Participants n=4 Participants	44 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=93 Participants	3 Participants n=4 Participants	10 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=93 Participants	27 Participants n=4 Participants	49 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	24 Participants n=93 Participants	28 Participants n=4 Participants	52 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	29 participants n=93 Participants	30 participants n=4 Participants	59 participants n=27 Participants

PRIMARY outcome

Timeframe: The duration of time from start of treatment to time of progression or death, assessed at 24 weeks

Outcome measures

Outcome measures
Measure	Arm I (Bevacizumab) n=29 Participants Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 Participants Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Progression-free Survival at 24 Weeks	52 percentage of participants Interval 36.0 to 76.0	27 percentage of participants Interval 15.0 to 50.0

PRIMARY outcome

Timeframe: The duration of time from start of treatment to time of progression or death, assessed at 12 weeks

Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.

Outcome measures

Outcome measures
Measure	Arm I (Bevacizumab) n=29 Participants Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 Participants Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Progression-free Survival at 12 Weeks	66 percentage of participants Interval 51.0 to 86.0	58 percentage of participants Interval 42.0 to 71.0

SECONDARY outcome

Timeframe: From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.

The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting. Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.

Outcome measures

Outcome measures
Measure	Arm I (Bevacizumab) n=29 Participants Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 Participants Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Abdominal pain	3 participants	3 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Bleeding	2 participants	0 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Fatigue	0 participants	2 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Hypertension	5 participants	4 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Anemia	4 participants	8 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Anorexia	0 participants	1 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment bronchopulmonary hemorrhage	1 participants	0 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Hypercalcemia	0 participants	2 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Hyponatremia	1 participants	2 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Infusion reaction	0 participants	2 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Nausea/vomitting	0 participants	5 participants
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment Proteinuria	2 participants	0 participants

SECONDARY outcome

Timeframe: From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Arm I (Bevacizumab) n=29 Participants Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 Participants Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Number of Participants With Overall Response	1 participants	1 participants

Adverse Events

Arm I (Bevacizumab)

Serious events: 10 serious events

Other events: 29 other events

Deaths: 4 deaths

Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)

Serious events: 14 serious events

Other events: 29 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Jeff Longmate, Ph.D.

City of Hope

Phone: 626-218-2478

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Bevacizumab) n=29 participants at risk Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 participants at risk Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Blood and lymphatic system disorders Anemia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Heart failure	6.9% 2/29 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Left ventricular systolic dysfunction	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Restrictive cardiomyopathy	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Ascites	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Duodenal hemorrhage	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Ileus	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Pancreatitis	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 3/30 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Death NOS	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Failure to thrive	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Infusion related reaction	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	6.9% 2/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Weakness	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Hepatobiliary disorders Hepatic failure	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Lung infection	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Skin infection	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Injury, poisoning and procedural complications Fall	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations progression of renal cell cancer	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Anorexia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperkalemia	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Bone pain	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive Disease	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events
Measure	Arm I (Bevacizumab) n=29 participants at risk Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) n=30 participants at risk Patients receive 10 mg\\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Blood and lymphatic system disorders Anemia	34.5% 10/29 • Number of events 29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	53.3% 16/30 • Number of events 79 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus bradycardia	10.3% 3/29 • Number of events 11 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 5/30 • Number of events 9 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus tachycardia	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 5/30 • Number of events 13 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Ear and labyrinth disorders Ear pain	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Ear and labyrinth disorders Vertigo	6.9% 2/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Blurred vision	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Glaucoma	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Itchy Eyes	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Watering eyes	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders suconjunctival hemorrhage	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal distension	6.9% 2/29 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 6 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	27.6% 8/29 • Number of events 11 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	13.3% 4/30 • Number of events 14 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Ascites	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Bloating	6.9% 2/29 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Blood in Stool	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	27.6% 8/29 • Number of events 13 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	26.7% 8/30 • Number of events 10 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	13.8% 4/29 • Number of events 6 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	23.3% 7/30 • Number of events 7 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 3/30 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Duodenal hemorrhage	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Flatulence	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastric hemorrhage	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gingival pain	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 3 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	6.9% 2/29 • Number of events 6 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	24.1% 7/29 • Number of events 9 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 10/30 • Number of events 16 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral dysesthesia	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral hemorrhage	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	13.3% 4/30 • Number of events 17 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	3.4% 1/29 • Number of events 2 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Periodontal disease	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Rectal discharge	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Stomach pain	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Tongue Ulcerations	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	13.8% 4/29 • Number of events 4 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	23.3% 7/30 • Number of events 9 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders diverticulosis	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders hiatal hernia	3.4% 1/29 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Bloody Gums	0.00% 0/29 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	13.8% 4/29 • Number of events 6 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 5 • Adverse events occurred over a period of 2 years and 7 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.