A Dose Escalation Study of R115777 (Zarnestra) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma.
OBJECTIVES: Primary I. Determine the maximum tolerated dose and dose-limiting toxicity of
tipifarnib when administered with bortezomib in patients with relapsed multiple myeloma.
(Phase I) II. Determine the response rate in patients treated with this regimen. (Phase II)
III. Determine the toxicity profile of this regimen in these patients. (Phase II)
Secondary I. Determine the progression-free survival of patients treated with this regimen.
Tertiary I. Determine whether this regimen overcomes CAM-DR in primary myeloma cells and
establish whether ex vivo efficacy predicts a clinical response in these patients.
II. Determine if activated Akt predicts clinical resistance and if levels of phosphorylated
Akt are reduced by tipifarnib and bortezomib in these patients.
III. Determine whether molecular profiles from primary isolates (suspension vs adhered)
correlate with clinical response in patients treated with this regimen.
OUTLINE: This is a phase I dose-escalation study of tipifarnib followed by a phase II study.
Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice
daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 52-64 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of tipifarnib as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (phase I)
Up to day 21
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
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