Phase I Study of Lonafarnib (SCH66336) in Combination With Herceptin Plus Paclitaxel in HER 2 NEU Overexpressing Breast Cancer
- Determine the maximum tolerated dose and recommended phase II dose of lonafarnib in
combination with trastuzumab (Herceptin®) and paclitaxel in patients with
HER2/neu-overexpressing stage IIIB, IIIC, or IV breast cancer.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
- Determine the pharmacokinetic profiles of these drugs in these patients.
- Correlate the pharmacodynamics with the pharmacokinetics of this regimen in these
- Correlate the pharmacokinetics and pharmacodynamics of this regimen with observed
toxicity in these patients.
- Determine the response to this regimen in patients with measurable disease.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of
- Course 1: Patients receive a loading dose of trastuzumab (Herceptin®) IV over 90
minutes on day 1 and over 30 minutes on days 8 and 15. Patients also receive paclitaxel
IV over 3 hours on day 1.
- Course 2: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 and
paclitaxel IV over 3 hours on day 2. Patients also receive oral lonafarnib twice daily
on days 3-21.
- Course 3 and all subsequent courses: Patients receive oral lonafarnib twice daily on
days 1-21; trastuzumab IV over 30 minutes on days 1, 8, and 15; and paclitaxel IV over
3 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of lonafarnib 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.
Patients are followed every 8 weeks until disease progression.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0
Jan H. M. Schellens, MD, PhD
The Netherlands Cancer Institute
United States: Federal Government