Lapatinib and Tamoxifen in Treating Patients With Advanced or Metastatic Breast Cancer - Full Text View

Sponsored by:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00424164

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: lapatinib ditosylate Drug: tamoxifen citrate Procedure: pharmacological study	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Lapatinib Lapatinib Ditosylate Tamoxifen Tamoxifen citrate Citric acid Sodium Citrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Relationship between drug exposure and adverse events or biological modifications [ Designated as safety issue: Yes ]
Response in patients with measurable disease [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2006

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424164

Locations

France
Centre Regional Rene Gauducheau	Recruiting
Dijon, France, 21079
Contact: Pierre Fumoleau, MD, PhD 33-3-8073-7506

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Study Chair:

Pierre Fumoleau, MD, PhD

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000524094, EORTC-10053, EUDRACT-2005-005196-14
Study First Received:	January 16, 2007
Last Updated:	August 14, 2008
ClinicalTrials.gov Identifier:	NCT00424164
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

male breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer

Study placed in the following topic categories:

Skin Diseases
Breast Neoplasms, Male
Citric Acid
Breast Neoplasms

Lapatinib
Tamoxifen
Breast Diseases
Recurrence

Additional relevant MeSH terms:

Estrogen Antagonists
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors

Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Protein Kinase Inhibitors
Pharmacologic Actions
Estrogen Receptor Modulators
Neoplasms
Neoplasms by Site
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009