Clinical trial NCT00323739: Bevacizumab (Avastin) and RAD001(Everolimus)in the Treatment of Advanced Clear Cell Renal Carcinoma
Official title: Phase II Trial of Bevacizumab(Avastin) and RAD001(Everolimus)in the Treatment of Patients With Advanced Clear Cell Renal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: kidney cancer
bevacizumab
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Novartis
First posted: 2006-05-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 18 months
Secondary outcomes:
measure: Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Gainsville Hematology Oncology Associates
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Louisville
country: United States
facility: Consultants in Blood Disorders and Cancer
state: Kentucky
city: Baton Rouge
country: United States
facility: Baton Rouge General Medical Center
state: Louisiana
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: John D. Hainsworth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hainsworth JD, Spigel DR, Burris HA 3rd, Waterhouse D, Clark BL, Whorf R. Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Clin Oncol. 2010 May 1;28(13):2131-6. doi: 10.1200/JCO.2009.26.3152. Epub 2010 Apr 5.