A Phase I Dose Escalation Study of a 2 Day Oral Lapatinib Chemosensitization Pulse Given Prior To Weekly Intravenous Abraxane™ in Patients With Advanced Solid Tumors
- Determine the maximum tolerated dose (MTD) of a 2-day pulse of lapatinib that can be
given prior to paclitaxel (albumin-stabilized nanoparticle formulation ) (ABI-007;
Abraxane™) in patients with advanced solid tumor malignancies.
- Define the toxicity of this regimen.
- Determine, preliminarily, the antitumor efficacy and safety of ABI-007 when preceded by
a 2-day pulse of lapatinib.
- Characterize the potential of the molecular markers within circulating tumor cells as
markers of response (e.g., HER2 and AKT) or apoptotic markers.
- Determine whether lapatinib given at MTD prior to ABI-007 alters the pharmacokinetic
properties of the paclitaxel component of ABI-007.
OUTLINE: This is a does-escalation study of lapatinib. Patients are stratified according to
Patients receive oral lapatinib on days 1, 2, 8, 9, 15, and 16 and paclitaxel
(albumin-stabilized nanoparticle formulation) (ABI-007; Abraxane™) IV over 30 minutes on
days 3, 10, and 17. Treatment repeats every 4 weeks in the absence of disease progression or
Cohorts of 1-6 patients receive escalating doses of lapatinib 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 toxicities.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of lapatinib in course 1
estimated to be 12 weeks
Mark M. Moasser, MD
University of California, San Francisco
United States: Food and Drug Administration
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|