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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: lapatinib ditosylate
• Drug: tamoxifen citrate
• Other: pharmacological study

Primary Measures

• Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination
  • Safety Issue?: No

Secondary Measures

• Safety
  • Safety Issue?: Yes
• Relationship between drug exposure and adverse events or biological modifications
  • Safety Issue?: Yes
• Response in patients with measurable disease
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: European Organization for Research and Treatment of Cancer

Overall Clinical Trial Officials and Contacts

Pierre Fumoleau, MD, PhD Study Chair Centre de Lutte Contre le Cancer Georges-Francois Leclerc  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00424164

Study ID Number: CDR0000524094

ClinicalTrials.gov Identifier: NCT00424164

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database