Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lung Cancer, Bladder Cancer, Brain and Central Nervous System Tumors, Breast Cancer, Esophageal Cancer, Extragonadal Germ Cell Tumor, Gastric Cancer, Ovarian Cancer, Prostate Cancer

Intervention / Treatment
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* Drug: lapatinib
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lapatinib and Paclitaxel<br>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<br> <br> * Other names: lapatinib ditosylate;Drug: paclitaxel<br> <br> * Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of lapatinib in course 1 |  | estimated to be 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, recurrent non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent prostate cancer, stage IV prostate cancer, recurrent bladder cancer, stage IV bladder cancer, recurrent gastric cancer, stage IV gastric cancer, recurrent esophageal cancer, stage IV esophageal cancer, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, adult central nervous system germ cell tumor, ovarian choriocarcinoma, ovarian dysgerminoma, ovarian embryonal carcinoma, ovarian yolk sac tumor, ovarian mixed germ cell tumor, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminoma, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, recurrent extragonadal germ cell tumor