Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination
Outcome Time Frame:
maximum 24h after the dose administered on Day 28
Safety Issue:
No
Principal Investigator
Pierre Fumoleau, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Authority:
United States: Federal Government
Study ID:
EORTC-10053
NCT ID:
NCT00424164
Start Date:
November 2006
Completion Date:
Related Keywords:
- Breast Cancer
- male breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- stage IV breast cancer
- recurrent breast cancer
- Breast Neoplasms
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