Kidney Cancer, Renal Cancer
Conditions
Keywords
Kidney Cancer, Renal Cancer, Clear Cell Carcinoma
Brief summary
This trial will examine the effectiveness and the side effects of 2 higher dosing schedules of bevacizumab in patients that have advanced clear cell renal carcinoma.
Detailed description
Bevacizumab is considered a targeted drug. Targeted drugs act on specific receptors on a cell. Bevacizumab blocks receptors that help cancer cells develop blood supplies so that the cancer can grow. These specific receptors are found in greater numbers in kidney cancer. In that regard bevacizumab will be tested in 2 doses that are higher than non-kidney cancer treatments with bevacizumab. One group of patients will receive bevacizumab at 15 mg per kg by vein every 2 weeks. A total of 75 patients will be treated with this dose. If this dose is well tolerated a second group of patients will receive bevacizumab at 15mg per kg by vein weekly.
Interventions
DRUGBevacizumab
Bevacizumab
Sponsors
Genentech, Inc.
SCRI Development Innovations, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented metastatic or unresectable locally recurrent clear cell renal carcinoma * Previous kidney removal is required except if the primary tumor was smaller than 5 cm or there was extensive liver or bone metastasis * Patients may have received a maximum of 1 prior systemic treatment of immunotherapy (Interferon, IL-2), chemotherapy, or combination chemo+immunotherapy for metastatic disease. * No prior bevacizumab * Measurable disease * Adequate liver and kidney function * Age 18 and older
Exclusion criteria
* Acute MI within the past 6 months * Uncontrolled high blood pressure or history of hypertensive crisis * Clinically significant cardiovascular disease * Active brain cancer * Meningeal metastasis * Pregnant or lactating women * Prior treatment for another cancer less than 5 years ago * No diseases of the central nervous system (eg. uncontrolled seizures, strokes or TIAs * No bleeding from the mouth, rectum or coughing up blood or history of other bleeding or clotting disorders * No history of deep vein thrombosis less than 12 months ago or are currently requiring full dose anticoagulation * No major surgical procedures, open biopsies or traumatic injury in past 28 days * No patients with peg tubes or feeding tubes * No patients with non healing wounds, ulcers or long bone fractures * No history of abdominal fistulas, gastrointestinal perforation or intrabdominal abscess within 6 months * No symptomatic peripheral vascular disease Please note: there are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 18 months | Measured from date of study entry to date of death due to any cause. |
| Objective Response Rate | 18 months | The 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 |
| Overall Tolerability and Toxicity of High-dose Bevacizumab | 18 months | Number of patients treated with high-dose bevacizumab experiencing Grade 3/4, treatment-related toxicities |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Weekly Avastin Bevacizumab 15mg/kg IV weekly until progressive disease or toxicity
Bevacizumab: Bevacizumab | 58 |
| Bi-weekly Avastin Bevacizumab 15mg/kg IV every 2 weeks until progressive disease or toxicity
Bevacizumab: Bevacizumab | 61 |
| Total | 119 |
Baseline characteristics
| Characteristic | Total | Bi-weekly Avastin | Weekly Avastin |
|---|---|---|---|
| Age, Continuous | 63 years | 60 years | 65 years |
| Region of Enrollment United States | 119 participants | 61 participants | 58 participants |
| Sex: Female, Male Female | 41 Participants | 17 Participants | 24 Participants |
| Sex: Female, Male Male | 78 Participants | 44 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 58 | 61 / 61 |
| serious Total, serious adverse events | 33 / 58 | 35 / 61 |
Outcome results
Primary
Progression-free Survival
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
Time frame: 18 months (expected)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Weekly Avastin | Progression-free Survival | 6.0 months |
| Bi-weekly Avastin | Progression-free Survival | 5.7 months |
Secondary
Objective Response Rate
The 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
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Weekly Avastin | Objective Response Rate | 9 participants |
| Bi-weekly Avastin | Objective Response Rate | 6 participants |
Secondary
Overall Survival (OS)
Measured from date of study entry to date of death due to any cause.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Weekly Avastin | Overall Survival (OS) | 26.9 months |
| Bi-weekly Avastin | Overall Survival (OS) | 18.4 months |
Secondary
Overall Tolerability and Toxicity of High-dose Bevacizumab
Number of patients treated with high-dose bevacizumab experiencing Grade 3/4, treatment-related toxicities
Time frame: 18 months
Population: All patients treated with Bevacizumab therapy were assessed for Grade 3/4 toxicities
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Proteinuria | 17 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Confusion | 0 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Arthralgia | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Allergic/hypersensitivity reaction | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Dyspnea | 4 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Hemorrhage | 3 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Thrombocytopenia | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Thrombosis/embolism | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Fatigue | 0 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Colitis | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Neuropathy/sensory | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Gastroenteritis | 0 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Nausea/vomiting | 0 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Renal failure | 0 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Hypertension | 13 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Myocardial infarction | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Anorexia | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Stroke | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Anemia | 2 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Tracheoesophageal fistula | 1 participants |
| Weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Headache | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Tracheoesophageal fistula | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Arthralgia | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Anemia | 5 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Thrombocytopenia | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Hypertension | 14 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Proteinuria | 12 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Dyspnea | 3 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Fatigue | 4 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Nausea/vomiting | 4 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Anorexia | 2 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Headache | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Confusion | 2 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Allergic/hypersensitivity reaction | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Hemorrhage | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Neuropathy/sensory | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Colitis | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Gastroenteritis | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Renal failure | 1 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Myocardial infarction | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Stroke | 0 participants |
| Bi-weekly Avastin | Overall Tolerability and Toxicity of High-dose Bevacizumab | Thrombosis/embolism | 3 participants |