Kidney Cancer
Conditions
Keywords
kidney cancer, bevacizumab
Brief summary
This phase II trial will evaluate the combination of bevacizumab + RAD001 in patients with metastatic renal cell carcinoma. In this trial the investigators will evaluate this combination in patients previously untreated with any anti-angiogenesis agent and patients who have previously received one prior regimen containing an anti-angiogenesis agent.
Detailed description
All eligible patients will receive: * Bevacizumab 10mg/kg, IV infusion, every 2 weeks * RAD001 10 mg by mouth daily All patients will be evaluated for response after completing two courses (8 weeks) of treatment. Patients with objective tumor response or stable disease will continue treatment with bevacizumab adn RAD001 on the same schedule. Treatment will continue until disease progression occurs.
Interventions
DRUGbevacizumab
Bevacizumab 10mg/kg, IV infusion, every 2 weeks
DRUGRAD001
RAD001 10 mg by mouth daily
Sponsors
Genentech, Inc.
Novartis
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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. * In patients with mixed histologies, the clear cell component must comprise ≥ 75% of the cancer * Previous nephrectomy is required with the following exceptions: * Primary tumor \< 5cm * Extensive liver ( \> 30% of liver parenchyma)or * Multiple (\> 5) bone metastases, making nephrectomy a clinically contraindicated procedure * Patients may have had a maximum of 1 previous systemic regimen for metastatic disease * Patients may not have received previous bevacizumab. However, patients who have received other agents with anti-angiogenic activity (eg. sorafenib, SU11248, AG-013736, PTK787, thalidomide) as part of first-line treatment are eligible * Patients may not have received previous treatment with m-TOR inhibitors. * ECOG performance status 0 or 1 * Measurable disease * Adequate liver, kidney and bone marrow function * No previous systemic treatment or radiation therapy for at least 2 weeks prior to study entry * Patients must be able to understand the nature of this study and give written informed consent
Exclusion criteria
* Age \< 18 years * Treatment with \> 1 previous systemic regimen for metastatic renal carcinoma * History of acute myocardial infarction within 6 months * Clinically significant cardiovascular disease * History of stroke within 6 months * Patients with active brain metastases * Patients with meningeal metastases * Women who are pregnant or lactating * Patients who have been treated within 5 years for other invasive cancers * Patients with history or evidence by physical examination of CNS disease * Patients with clinical history of hemoptysis or hematemesis * Patients with history of deep vein thrombosis or thromboembolic disease requiring full dose anticoagulation * Patients with major surgical procedures, open biopsies, or significant traumatic injuries within 28 days or anticipated need for major surgical procedure during the course of the study * Patients with peg-tubes or G-tubes * Patients are ineligible if a fine needle aspiration biopsy has been performed within seven days * Patients with proteinuria * Patients with any non-healing wound, ulcer, or long-bone fracture * Patients with any history of a bleeding diathesis or coagulopathy * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months * Patients who have received any other experimental drug within 28 days of starting treatment * History of any other severe and/or uncontrolled medical disease * History of HIV infection * Chronic treatment with steroids or other immunosuppressive agents * Patients with impaired GI function that compromises the ability to swallow or absorb RAD001 * Patients who are unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 18 months |
Countries
United States
Participant flow
Recruitment details
Eighty-four patients with advanced kidney cancer were assessed for participation at multiple US clinics between August 2006 and November 2008.
Pre-assignment details
Four patients did not meet eligibility criteria and were not treated.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab and Everolimus Patients received 10mg/kg of bevacizumab by IV infusion on day 1 and day 15 of each 28-day treatment cycle. Patients took 1 10mg tablet of everolimus every day for 28 days. Treatment continued until evidence of their disease worsening was found or until the side effects of treatment became intolerable to the patient. The treating physician could also stop treatment if the patient's safety was felt to be at risk. | 80 |
| Total | 80 |
Baseline characteristics
| Characteristic | Bevacizumab and Everolimus |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 38 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age Continuous | 64 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment United States | 80 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 62 / 80 |
| serious Total, serious adverse events | 25 / 80 |
Outcome results
Primary
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab and Everolimus | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 8.1 Months |
Secondary
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab and Everolimus | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 18.5 Months |