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

March 7, 2024 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Dijon, France, 21079
        • Centre Regional Rene Gauducheau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tamoxifen-lapatinib
Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib.
Other: pharmacological study
Drug: tamoxifen citrate
Drug: lapatinib ditosylate
Experimental: 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
Other: pharmacological study
Drug: tamoxifen citrate
Drug: lapatinib ditosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination
Time Frame: maximum 24h after the dose administered on Day 28
maximum 24h after the dose administered on Day 28

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety
Time Frame: until disease progression or until the start of another treatment (average 2 months)
until disease progression or until the start of another treatment (average 2 months)
Relationship between drug exposure and adverse events or biological modifications
Time Frame: until disease progression or until the start of another treatment (average 2 months)
until disease progression or until the start of another treatment (average 2 months)
Response in patients with measurable disease
Time Frame: until disease progression or until the start of another treatment (average 2 months)
until disease progression or until the start of another treatment (average 2 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Pierre Fumoleau, MD, PhD, Centre Georges Francois Leclerc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

May 28, 2010

Study Registration Dates

First Submitted

January 16, 2007

First Submitted That Met QC Criteria

January 16, 2007

First Posted (Estimated)

January 18, 2007

Study Record Updates

Last Update Posted (Actual)

March 8, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-10053
  • 2005-005196-14 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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