Clinical Trial: Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may help paclitaxel work better by making tumor cells more sensitive to the drug. Lapatinib may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving lapatinib together with paclitaxel may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with paclitaxel in treating patients with advanced solid tumors.


Detailed Summary:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 dose level.

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 unacceptable toxicity.

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
Sponsor: University of California, San Francisco

Current Primary Outcome: Maximum tolerated dose (MTD) of lapatinib in course 1 [ Time Frame: estimated to be 12 weeks ]

Original Primary Outcome:

Current Secondary Outcome:

  • Toxicity [ Time Frame: up to 12 weeks ]
  • Anti-tumor efficacy and safety every 8 weeks [ Time Frame: until disease progression estimated to be 12 weeks ]
  • Pharmacokinetics during the first 2 weeks of treatment [ Time Frame: 2 weeks ]


Original Secondary Outcome:

Information By: University of California, San Francisco

Dates:
Date Received: April 11, 2006
Date Started: February 2006
Date Completion:
Last Updated: July 1, 2014
Last Verified: July 2014