Phase I Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose of erlotinib in combination with tipifarnib in
patients with advanced solid tumors.
II. Determine the toxicity profile of this regimen in these patients. III. Determine the
effect of erlotinib on the disposition of tipifarnib in these patients.
IV. Determine in vitro markers of farnesyl transferase inhibition and epidermal growth
factor receptor inhibition in patients treated with this regimen.
OUTLINE: This is a dose-escalation study.
Patients receive oral erlotinib once daily on days 1-28 and oral tipifarnib twice daily on
days 1-21. Courses repeat every 28 days in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of erlotinib and tipifarnib 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 (closed to accrual as of
Once the MTD is determined, up to 12 additional patients are treated at that dose. Patients
receive oral tipifarnib as above and oral erlotinib once daily on days 1-28 (days 8-28 of
course 1 only). Courses repeat every 28 days in the absence of disease progression or
Patients are followed at 3 months.
PROJECTED ACCRUAL: A total of 18-42 patients (12 treated at the maximum tolerated dose) will
be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number and severity of all adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Up to 30 days after last study treatment
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|