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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00424164
First received: January 16, 2007
Last updated: June 18, 2013
Last verified: June 2013
  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
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination [ Time Frame: maximum 24h after the dose administered on Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Time Frame: until disease progression or until the start of another treatment (average 2 months) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]
  • Response in patients with measurable disease [ Time Frame: until disease progression or until the start of another treatment (average 2 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2006
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tamoxifen-lapatinib
Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib.
Drug: lapatinib ditosylate Drug: tamoxifen citrate Other: pharmacological study
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
Drug: lapatinib ditosylate Drug: tamoxifen citrate Other: pharmacological study

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
France
Centre Regional Rene Gauducheau
Dijon, France, 21079
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Pierre Fumoleau, MD, PhD Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00424164     History of Changes
Other Study ID Numbers: EORTC-10053, 2005-005196-14
Study First Received: January 16, 2007
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
male breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib
Tamoxifen
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 16, 2014