Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00313599

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Brain and Central Nervous System Tumors Breast Cancer Esophageal Cancer Extragonadal Germ Cell Tumor Gastric Cancer Lung Cancer Ovarian Cancer Prostate Cancer	Drug: lapatinib Drug: paclitaxel	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Feb 1, 2006

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lapatinib and 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.	Drug: lapatinib Other Names: Tykerb Tyverb lapatinib ditosylate Drug: paclitaxel Other Names: paclitaxel albumin-stabilized nanoparticle formulation Abraxane Taxol

Arm

Intervention/Treatment

Experimental: Lapatinib and 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.

Drug: lapatinib

Other Names:

Tykerb

Tyverb

lapatinib ditosylate

Drug: paclitaxel

Other Names:

paclitaxel albumin-stabilized nanoparticle formulation

Abraxane

Taxol

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) of lapatinib in course 1 [estimated to be 12 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor, including the following tumor types:
Breast cancer
Non-small cell lung cancer
Prostate cancer
Bladder cancer
Gastroesophageal junction cancer
Ovarian cancer
Germ cell tumor
Advanced or metastatic disease
No effective curative therapy exists
Evaluable disease
Measurable disease not required
Bone-only disease allowed
No progressing brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 3 months
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 9.0 g/dL
Platelet count ≥ 100,000/mm^3
Bilirubin normal
AST/ALT ≤ 2.5 times upper limit of normal
Creatinine normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No serious intercurrent medical or psychiatric illness
No serious active infection
No gastrointestinal tract disease that would impair a patient's ability to take oral medication
No history of significant cardiac disease, including any of the following:
Congestive heart failure
Symptomatic cardiac arrhythmias
Unstable angina
No pre-existing peripheral neuropathy ≥ 2

PRIOR CONCURRENT THERAPY:

Any number of prior therapies allowed
Prior paclitaxel, tyrosine kinase inhibitor therapy, or endothelial growth factor inhibitors allowed
At least 14 days since prior and no concurrent CYP3A4 inducers or herbal or dietary supplements
At least 7 days since prior and no concurrent CYP3A4 inhibitors
At least 6 months since prior and no concurrent amiodarone
More than 1 month since prior chemotherapy, radiotherapy, hormonal therapy, or investigational anticancer agents
Concurrent continued use of gonadal suppression agents (i.e., goserelin acetate or leuprolide acetate) allowed
No antacids 1 hour before and after study drug administration
No concurrent retinoids
No concurrent hormonal anticancer agent
No other concurrent anticancer chemotherapy or investigational anticancer agents