Phase II Evaluation of FTI (R115777) (NSC 702818) in Treatment of Advanced Multiple Myeloma
OBJECTIVES: I. Determine the rate of objective response and disease stabilization in
patients with relapsed or refractory multiple myeloma treated with R115777. II. Determine
whether the degree of inhibition of FTase activity and farnesylation of lamin-B, H-, K-, and
N-RAS in peripheral blood mononuclear cells and tumor tissue correlates with tumor response
in patients treated with this regimen. III. Determine whether the presence of activating RAS
mutations in myeloma cells predicts treatment response in patients treated with this
regimen. IV. Correlate R115777 plasma levels and RAS mutation status with tumor response in
patients treated with this regimen.
OUTLINE: Patients receive oral R115777 twice daily on days 1-21. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity. Patients are followed
for at least 30 days.
PROJECTED ACCRUAL: Approximately 12-42 patients will be accrued for this study within 25
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response Rate (ORR)
The primary end point of the study is to determine the rate of objective response and disease stabilization. Responses were to be defined according to modified Southwest Oncology Group (SWOG) criteria. Disease progression was defined as a 25% increase in the serum M-component confirmed by a second measurement obtained within 1 to 4 weeks of the first measurement, or an increase in the 24-hour urine M-component by more than 50%, confirmed by a second measurement. Other criteria for disease progression included the need to administer radiotherapy, new lytic bone lesions, enlargement of existing bone lesions, or new soft tissue plasmacytomas.
Melissa Alsina, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|