Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Lung Cancer; Esophageal Cancer; Extragonadal Germ Cell Tumor; Bladder Cancer; Ovarian Cancer; Prostate Cancer; Brain and Central Nervous System Tumors; Breast Cancer; Gastric Cancer
• Interventions: Drug: lapatinib; Drug: paclitaxel

• Registration Number: NCT00313599
• Lead Sponsor: University of California, San Francisco

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 Description

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 accrued for this study.

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2006-04-11
• Study First Submitted QC: 2006-04-11
• Study First Posted: 2006-04-12
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-01
• Last Update Posted: 2014-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lapatinib and Paclitaxel	lapatinib	Lapatinib will be self-administered orally on days 1 and 2 of weeks 1, 2, and 3 of a 4-week cycle. Lapatinib is the experimental therapy and is being administered using a dose escalation design guided by careful monitoring of toxicities. Abraxane will be administered IV weekly on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Abraxane is being administered at the well tolerated and effective standard dose and schedule of 100mg/m2 weekly 3 out of 4 weeks as defined by previous phase I and II studies. Patients will continue on therapy as long as they are not experiencing toxicities and there is no evidence of disease progression.
Lapatinib and Paclitaxel	paclitaxel	Lapatinib will be self-administered orally on days 1 and 2 of weeks 1, 2, and 3 of a 4-week cycle. Lapatinib is the experimental therapy and is being administered using a dose escalation design guided by careful monitoring of toxicities. Abraxane will be administered IV weekly on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Abraxane is being administered at the well tolerated and effective standard dose and schedule of 100mg/m2 weekly 3 out of 4 weeks as defined by previous phase I and II studies. Patients will continue on therapy as long as they are not experiencing toxicities and there is no evidence of disease progression.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of lapatinib in course 1	estimated to be 12 weeks

Secondary Outcome Measures

Name	Time	Method
Toxicity	up to 12 weeks
Anti-tumor efficacy and safety every 8 weeks	until disease progression estimated to be 12 weeks
Pharmacokinetics during the first 2 weeks of treatment	2 weeks

Trial Locations

Locations (1)

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States