A Single Arm, Phase Ib Study of RAD001 and Sunitinib in Patients With Advanced Renal Cell Carcinoma
Escalation of both drugs will occur as tolerated. Treatment will be arbitrarily divided
into 3-week cycles, with dose limiting toxicity (DLT) determined by Cycle 2 Day 0. Dose
levels will be evaluated one at a time beginning with 3 patients. If 1/3 patients
demonstrate DLT (as defined in section Complete), then enrollment will proceed to the next
dose level. 1/3 patients develops a DLT, then 3 more patients will be accrued to this dose
level. If 0-1/6 patients demonstrate DLT, then enrollment will proceed to the next dose
level. However, if 2 or more patients out of 6 demonstrate DLT at a dose level, then
enrollment will proceed at the next lowest dose level. The highest dose level not resulting
in greater than 1/6 DLT will be considered the MTD. Dose expansion will then proceed at
this dose level.
Once the maximum tolerated dose has been established for this regimen a dose expansion of 20
patients with metastatic RCC will be undertaken. Up to 10 patients with a positive FDG- PET
scan at baseline (defined by 1 or more target lesions demonstrating an SUV > 5.0) will begin
treatment per Figure 2B. Patients 1-10 will begin Sunitinib on Day 0 and begin RAD001 on
Day 14 after repeat FDG-PET scan. Patients 11-20, will have a 2 week lead-in period of
RAD001 and will begin Sunitinib 2 weeks later on Day 0. After repeat FDG-PET scan. Both
groups of patients will repeat PET scan at Day 14 of cycle 2. Patients with negative FDG
PET scans (SUV < 5.0 in all lesions) will not undergo repeat scanning. Patients will undergo
evaluations for tumor response every 12 weeks with appropriate measurement studies (CT, MRI,
bone scan). In the setting of a mixed response (progressive disease in 1 or more lesions
but continued regression or stable disease below baseline in other lesions) patients may
continue on study if it is determined by the PI, treating physician and patient that there
is ongoing clinical benefit to the patient.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD)/recommended Phase 2 regimen of 2+1 dosing with Sunitinib and daily RAD001 in patients with advanced renal cell carcinoma.
Daniel J. George, M.D.
United States: Food and Drug Administration
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