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

NCT ID: NCT00424164

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2010-05-28

Brief Summary

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

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tamoxifen-lapatinib

Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib.

Group Type: EXPERIMENTAL

lapatinib ditosylate

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Lapatinib-tamoxifen

Lapatinib will be given alone for 2 weeks during cycle 1. As of cycle 2, you will receive the combined treatment Lapatinib and Tamoxifen

Group Type: EXPERIMENTAL

lapatinib ditosylate

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Interventions

lapatinib ditosylate

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre Fumoleau, MD, PhD

Role: STUDY_CHAIR

Centre Georges Francois Leclerc

Locations

Centre Regional Rene Gauducheau

Dijon, , France

Countries

France

References

Fumoleau P, Koch KM, Brain E, Lokiec F, Rezai K, Awada A, Hayward L, Werutsky G, Bogaerts J, Marreaud S, Cardoso F. A phase I pharmacokinetics study of lapatinib and tamoxifen in metastatic breast cancer (EORTC 10053 Lapatam study). Breast. 2014 Oct;23(5):663-9. doi: 10.1016/j.breast.2014.07.003. Epub 2014 Jul 24.

Reference Type: DERIVED

PMID: 25065668 (View on PubMed)

Other Identifiers

2005-005196-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-10053

Identifier Type: -

Identifier Source: org_study_id