Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Closed	Over 18	Other	EORTC-10053 EUDRACT-2005-005196-14, NCT00424164

Objectives

Primary

1. Determine the pharmacokinetics of lapatinib ditosylate and tamoxifen citrate in patients with advanced or metastatic breast cancer.

Secondary

1. Assess the safety of this regimen in these patients.
2. Determine any relationship between drug exposure and adverse events or biological modifications of this regimen in these patients.
3. Assess the antitumor activity of this regimen in patients with measurable disease.

Entry Criteria

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

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

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

Expected Enrollment

A total of 20 patients will be accrued for this study.

Outcomes

Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination

Safety
Relationship between drug exposure and adverse events or biological modifications
Response 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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Pierre Fumoleau, MD, PhD, Protocol chair		Ph: 33-3-8073-7506

Registry Information
Official Title		Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer
Trial Start Date		2006-11-15
Registered in ClinicalTrials.gov		NCT00424164
Date Submitted to PDQ		2006-11-30
Information Last Verified		2009-02-10

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