Trial Outcomes & Findings for High-dose Bevacizumab in Advanced Renal Carcinoma Patients (NCT NCT00455975)
NCT ID: NCT00455975
Last Updated: 2014-12-22
Results Overview
Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in 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
119 participants
Primary outcome timeframe
18 months (expected)
Results posted on
2014-12-22
Participant Flow
Participant milestones
| Measure |
Weekly Avastin
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
61
|
|
Overall Study
COMPLETED
|
40
|
40
|
|
Overall Study
NOT COMPLETED
|
18
|
21
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
High-dose Bevacizumab in Advanced Renal Carcinoma Patients
Baseline characteristics by cohort
| Measure |
Weekly Avastin
n=58 Participants
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 Participants
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Total
n=119 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
60 years
n=7 Participants
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 participants
n=5 Participants
|
61 participants
n=7 Participants
|
119 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 months (expected)Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in 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
| Measure |
Weekly Avastin
n=58 Participants
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 Participants
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Progression-free Survival
|
6.0 months
Interval 3.5 to 9.1
|
5.7 months
Interval 3.6 to 9.2
|
SECONDARY outcome
Timeframe: 18 monthsMeasured from date of study entry to date of death due to any cause.
Outcome measures
| Measure |
Weekly Avastin
n=58 Participants
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 Participants
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Overall Survival (OS)
|
26.9 months
Interval 12.9 to
Upper bound of 95% confidence interval not reached at this time point
|
18.4 months
Interval 12.0 to 28.9
|
SECONDARY outcome
Timeframe: 18 monthsThe number of patients with observed complete response \[CR\] or partial response \[PR\]. 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; Objective Response (OR) = CR + PR
Outcome measures
| Measure |
Weekly Avastin
n=58 Participants
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 Participants
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Objective Response Rate
|
9 participants
|
6 participants
|
SECONDARY outcome
Timeframe: 18 monthsPopulation: All patients treated with Bevacizumab therapy were assessed for Grade 3/4 toxicities
Number of patients treated with high-dose bevacizumab experiencing Grade 3/4, treatment-related toxicities
Outcome measures
| Measure |
Weekly Avastin
n=58 Participants
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 Participants
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Anemia
|
2 participants
|
5 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Thrombocytopenia
|
1 participants
|
0 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Hypertension
|
13 participants
|
14 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Proteinuria
|
17 participants
|
12 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Dyspnea
|
4 participants
|
3 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Fatigue
|
0 participants
|
4 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Nausea/vomiting
|
0 participants
|
4 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Anorexia
|
1 participants
|
2 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Headache
|
1 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Confusion
|
0 participants
|
2 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Allergic/hypersensitivity reaction
|
1 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Hemorrhage
|
3 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Thrombosis/embolism
|
1 participants
|
3 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Arthralgia
|
1 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Neuropathy/sensory
|
1 participants
|
0 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Colitis
|
1 participants
|
0 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Gastroenteritis
|
0 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Renal failure
|
0 participants
|
1 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Myocardial infarction
|
1 participants
|
0 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Stroke
|
1 participants
|
0 participants
|
|
Overall Tolerability and Toxicity of High-dose Bevacizumab
Tracheoesophageal fistula
|
1 participants
|
0 participants
|
Adverse Events
Weekly Avastin
Serious events: 33 serious events
Other events: 58 other events
Deaths: 0 deaths
Bi-weekly Avastin
Serious events: 35 serious events
Other events: 61 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Weekly Avastin
n=58 participants at risk
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 participants at risk
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
3.4%
2/58
|
3.3%
2/61
|
|
General disorders
General disorders and administration site conditions - Other, disease progression
|
3.4%
2/58
|
3.3%
2/61
|
|
Gastrointestinal disorders
Nausea
|
1.7%
1/58
|
1.6%
1/61
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.4%
2/58
|
1.6%
1/61
|
|
Vascular disorders
Thromboembolic event
|
3.4%
2/58
|
1.6%
1/61
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/58
|
4.9%
3/61
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/58
|
1.6%
1/61
|
|
Blood and lymphatic system disorders
Anemia
|
1.7%
1/58
|
0.00%
0/61
|
|
Psychiatric disorders
Confusion
|
1.7%
1/58
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.7%
1/58
|
1.6%
1/61
|
|
Injury, poisoning and procedural complications
Fracture
|
1.7%
1/58
|
1.6%
1/61
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
3.4%
2/58
|
0.00%
0/61
|
|
Vascular disorders
Hypertension
|
0.00%
0/58
|
3.3%
2/61
|
|
General disorders
Non-cardiac chest pain
|
1.7%
1/58
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.7%
1/58
|
1.6%
1/61
|
|
Psychiatric disorders
Psychiatric disorders - Other, change in mental status
|
0.00%
0/58
|
3.3%
2/61
|
|
Nervous system disorders
Stroke
|
0.00%
0/58
|
3.3%
2/61
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
1/58
|
1.6%
1/61
|
|
Metabolism and nutrition disorders
Anorexia
|
1.7%
1/58
|
0.00%
0/61
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/58
|
1.6%
1/61
|
|
Infections and infestations
Bone infection
|
0.00%
0/58
|
1.6%
1/61
|
|
Cardiac disorders
Cardiac disorders - Other, ischemia
|
1.7%
1/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/58
|
1.6%
1/61
|
|
General disorders
Death NOS
|
1.7%
1/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Dysphagia
|
1.7%
1/58
|
0.00%
0/61
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/58
|
1.6%
1/61
|
|
Gastrointestinal disorders
Esophageal fistula
|
1.7%
1/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Gastritis
|
1.7%
1/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, hemorrhage
|
1.7%
1/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, small bowel obstruction
|
0.00%
0/58
|
1.6%
1/61
|
|
General disorders
General disorders and administration site conditions - Other, failure to thrive
|
1.7%
1/58
|
0.00%
0/61
|
|
Cardiac disorders
Heart Failure
|
0.00%
0/58
|
1.6%
1/61
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
1.7%
1/58
|
0.00%
0/61
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.7%
1/58
|
0.00%
0/61
|
|
Infections and infestations
Infections and infestations - Other, gastroenteritis
|
0.00%
0/58
|
1.6%
1/61
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
0.00%
0/58
|
1.6%
1/61
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders - Other, lumbar spondylosis
|
0.00%
0/58
|
1.6%
1/61
|
|
Cardiac disorders
Myocardial Infarction
|
1.7%
1/58
|
0.00%
0/61
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/58
|
1.6%
1/61
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, renal failure
|
1.7%
1/58
|
0.00%
0/61
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, chronic lung disease
|
0.00%
0/58
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, COPD exacerbation
|
0.00%
0/58
|
1.6%
1/61
|
|
Cardiac disorders
Sinus bradycardia
|
1.7%
1/58
|
0.00%
0/61
|
|
Nervous system disorders
Tremor
|
1.7%
1/58
|
0.00%
0/61
|
|
Renal and urinary disorders
Urinary tract obstruction
|
1.7%
1/58
|
0.00%
0/61
|
Other adverse events
| Measure |
Weekly Avastin
n=58 participants at risk
Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
Bi-weekly Avastin
n=61 participants at risk
Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab
|
|---|---|---|
|
General disorders
FATIGUE
|
63.8%
37/58
|
82.0%
50/61
|
|
Renal and urinary disorders
PROTEINURIA
|
58.6%
34/58
|
63.9%
39/61
|
|
Gastrointestinal disorders
NAUSEA
|
36.2%
21/58
|
36.1%
22/61
|
|
Metabolism and nutrition disorders
Anorexia
|
24.1%
14/58
|
39.3%
24/61
|
|
Nervous system disorders
HEADACHE
|
31.0%
18/58
|
27.9%
17/61
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
27.6%
16/58
|
27.9%
17/61
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.7%
12/58
|
31.1%
19/61
|
|
Vascular disorders
HYPERTENSION
|
51.7%
30/58
|
0.00%
0/61
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.5%
9/58
|
34.4%
21/61
|
|
Gastrointestinal disorders
Constipation
|
17.2%
10/58
|
26.2%
16/61
|
|
Gastrointestinal disorders
VOMITING
|
13.8%
8/58
|
24.6%
15/61
|
|
Gastrointestinal disorders
Abdominal pain
|
12.1%
7/58
|
24.6%
15/61
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.8%
8/58
|
19.7%
12/61
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
8.6%
5/58
|
21.3%
13/61
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
10.3%
6/58
|
18.0%
11/61
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/58
|
26.2%
16/61
|
|
General disorders
Fever
|
8.6%
5/58
|
18.0%
11/61
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.6%
5/58
|
18.0%
11/61
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/58
|
24.6%
15/61
|
|
General disorders
Edema limbs
|
0.00%
0/58
|
21.3%
13/61
|
|
Immune system disorders
Allergic reaction
|
6.9%
4/58
|
14.8%
9/61
|
|
Psychiatric disorders
Insomnia
|
6.9%
4/58
|
14.8%
9/61
|
|
Nervous system disorders
Dizziness
|
0.00%
0/58
|
19.7%
12/61
|
|
Metabolism and nutrition disorders
hyperkalemia
|
0.00%
0/58
|
18.0%
11/61
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/58
|
16.4%
10/61
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
8.6%
5/58
|
8.2%
5/61
|
|
Gastrointestinal disorders
Oral pain
|
6.9%
4/58
|
9.8%
6/61
|
|
General disorders
Chills
|
6.9%
4/58
|
9.8%
6/61
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.5%
9/58
|
0.00%
0/61
|
|
Investigations
Creatinine increased
|
0.00%
0/58
|
14.8%
9/61
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.2%
3/58
|
9.8%
6/61
|
|
General disorders
Edema
|
6.9%
4/58
|
8.2%
5/61
|
|
Psychiatric disorders
Depression
|
5.2%
3/58
|
9.8%
6/61
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/58
|
13.1%
8/61
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, urinary hemorrhage
|
5.2%
3/58
|
8.2%
5/61
|
|
General disorders
Non-cardiac chest pain
|
1.7%
1/58
|
11.5%
7/61
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/58
|
11.5%
7/61
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/58
|
11.5%
7/61
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, sinus drainage
|
0.00%
0/58
|
11.5%
7/61
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/58
|
9.8%
6/61
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
8.6%
5/58
|
0.00%
0/61
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/58
|
8.2%
5/61
|
|
Investigations
Weight loss
|
0.00%
0/58
|
8.2%
5/61
|
|
Infections and infestations
Rhinitis infective
|
3.4%
2/58
|
4.9%
3/61
|
|
Nervous system disorders
Tremor
|
5.2%
3/58
|
3.3%
2/61
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
- Publication restrictions are in place
Restriction type: OTHER