Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

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.

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