Lapatinib and Tamoxifen in Treating Patients With Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving lapatinib together with tamoxifen may be an effective treatment for breast cancer. PURPOSE: This randomized phase I trial is studying the side effects of lapatinib and tamoxifen in treating patients with advanced or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the pharmacokinetics of lapatinib ditosylate and tamoxifen citrate in patients with advanced or metastatic breast cancer. Secondary Assess the safety of this regimen in these patients. Determine any relationship between drug exposure and adverse events or biological modifications of this regimen in these patients. Assess the antitumor activity of this regimen in patients with measurable disease. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen citrate on days 1-28 of course 1. In all subsequent courses, patients receive oral tamoxifen citrate and oral lapatinib ditosylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral lapatinib ditosylate on days 1-14 of course 1. In all subsequent courses, patients receive oral lapatinib ditosylate and oral tamoxifen citrate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. In both treatment arms, blood is collected periodically during courses 1 and 2 for pharmacokinetic studies. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: lapatinib ditosylate
* Drug: tamoxifen citrate
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced or metastatic breast cancer Progressive disease after aromatase inhibitor therapy Hormone receptor status: Estrogen receptor- and/or progesterone receptor-positive tumor Patients with stable brain metastases (i.e., no neurological symptoms and no corticosteroid treatment) are eligible PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 12 weeks Neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ AST and/or ALT < 3 times upper limit of normal (ULN) Creatinine < 1.5 times ULN Bilirubin < 1.5 times ULN Clinically normal cardiac function (i.e., LVEF normal by MUGA or ECHO) No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic live disease) No ischemic heart disease within the past 6 months Normal 12-lead ECG No active or uncontrolled infections No serious illnesses or medical conditions, including any of the following: Hypercalcemia Malabsorption syndrome Chronic alcohol abuse Hepatitis HIV Cirrhosis Able to swallow and retain oral medication No psychological, familial, sociological, or geographical condition potentially hampering study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 days since prior and no concurrent inducers or inhibitors of CYP3A4, including any of the following: Rifabutin Clarithromycin Cyclosporine Voriconazole Fluoxetine Paroxetine Midazolam Isoniazid Dihydralazine Digitoxin Coumadin Phenytoin Verapamil Diltiazem Herbal constituents (e.g., bergamottin and glabridin) At least 2 weeks since prior aromatase inhibitor Aromatase inhibitors in the adjuvant and/or metastatic setting allowed At least 1 year since prior tamoxifen citrate No other concurrent anticancer therapy or investigational 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen-lapatinib<br>Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib. | Drug: lapatinib ditosylate<br> <br> Drug: tamoxifen citrate<br> <br> Other: pharmacological study<br> <br> |
| Experimental: Lapatinib-tamoxifen<br>Lapatinib will be given alone for 2 weeks during cycle 1. As of cycle 2, you will receive the combined treatment Lapatinib and Tamoxifen | Drug: lapatinib ditosylate<br> <br> Drug: tamoxifen citrate<br> <br> Other: pharmacological study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination |  | maximum 24h after the dose administered on Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | until disease progression or until the start of another treatment (average 2 months) | 
| Relationship between drug exposure and adverse events or biological modifications |  | until disease progression or until the start of another treatment (average 2 months) | 
| Response in patients with measurable disease |  | until disease progression or until the start of another treatment (average 2 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer