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