A Phase I/II Trial of CCI-779 and Bevacizumab in Stage IV Renal Cell Carcinoma
I. To determine the maximally tolerated dose (MTD) and recommended dosing for the
combination of CCI-779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase
I) II. To determine the proportion of patients with metastatic renal cell cancer who are
progression free at 6 months. (Phase II)
I. To determine the toxicity of the combination of CCI 779 and Bevacizumab in patients with
metastatic renal cell cancer. (Phase II) II. To determine the clinical response rate of CCI
779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase II) III. To
determine the time to progression (TTP), disease free survival, and overall survival of CCI
779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase II)
I. To identify predictive molecular markers of response, both at the tumor level and in the
plasma/serum level, in an exploratory manner.
II. To correlate blood markers of angiogenesis with clinical activity of the combination of
CCI-779 and Bevacizumab.
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.
Patients are stratified according to study phase (I vs II).
Phase I: Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of CCI-779 and bevacizumab until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients
receive CCI-779 and bevacizumab as in phase I at the MTD determined in phase I. After
completion of study treatment, patients are followed every 3 months until disease
progression and then every 6 months for up to 3 years after study entry.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (DLT) (Phase I)
Hematologic DLT measures will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via Common Terminology Criteria for Adverse Events (CTCAE) version 3 standard toxicity grading. Non-hematologic DLTs such as dyspnea and renal will be evaluated via CTCAE only. The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose where ≤1 out of 6 patients experience DLT with the next higher dose having at least 2 patients who experience DLT.
Patients observed a minimum of 4 weeks (one full course) for each dose level.
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|