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Lapatinib in Treating Patients With Advanced or Metastatic Breast Cancer That Overexpresses HER2

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco Identifier:
First received: October 13, 2007
Last updated: July 1, 2014
Last verified: July 2014

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib in treating patients with advanced or metastatic breast cancer that overexpresses HER2.

Condition Intervention Phase
Breast Cancer
Metastatic Cancer
Drug: lapatinib ditosylate
Genetic: gene expression analysis
Other: diagnostic laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer

Resource links provided by NLM:

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Maximum tolerated dose of Lapatinib [ Time Frame: estimated to be 12 months ]
    Dose Escalation of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer

Enrollment: 41
Study Start Date: August 2007
Study Completion Date: December 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib
Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
Drug: lapatinib ditosylate Genetic: gene expression analysis Other: diagnostic laboratory biomarker analysis

Detailed Description:



  • To determine the maximum tolerated dose (MTD) of high-dose lapatinib ditosylate in patients with HER2-overexpressing advanced or metastatic breast cancer.
  • To determine the dose-limiting toxicity of this drug in these patients.


  • To determine whether tumor HER2 can be completely inactivated by lapatinib ditosylate at its MTD in the 5-day schedule.
  • To determine whether the total inactivation of HER2 decreases cardiac ejection fraction.

OUTLINE: Patients are stratified according to dose level.

Patients receive escalating doses of oral lapatinib ditosylate twice daily on days 1-5 until the maximum tolerated dose is determined. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Some patients undergo tumor tissue and blood sample collection periodically for biological and correlative studies. Samples are analyzed for evidence of cardiac injury, tumor target lysis effects, and to determine if the lapatinib serum levels result in the inactivation of tumor HER2 and HER3 kinase and oncogenic signaling.

After completion of study treatment, patients are followed every 2 months.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed breast cancer

    • Advanced or metastatic disease
    • No effective curative therapy available
  • Bone-only disease allowed
  • Tumor HER2 overexpression

    • HER2 3+ expression by immunohistochemistry OR > 2-fold (HER2 2+) gene amplification by fluorescence in situ hybridization
  • Evaluable disease

    • Measurable disease is not required
  • No progressive brain metastases
  • Hormone receptor status not specified


Inclusion criteria:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • Female
  • Menopausal status not specified
  • Absolute neutrophil count ≥ 1,000 cells/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 75,000 cells/mm^3
  • Total bilirubin normal
  • AST and ALT ≤ 3 x upper limits of normal (ULN) (≤ 5 x ULN with liver metastases)
  • Creatinine normal OR creatinine clearance ≥ 40 mL/min
  • INR ≤ 1.5
  • Potassium normal
  • Magnesium normal
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during study therapy
  • Cardiac ejection fraction ≥ 50%
  • Consents to 2 tumor fine needle aspiration biopsies for biomarker analysis

    • Lung-only disease or sites otherwise deemed high-risk for biopsy, the requirement for biopsy will be waived

Exclusion criteria:

  • History of significant cardiac disease including any of the following:

    • Congestive heart failure
    • Symptomatic cardiac arrhythmias
    • Unstable angina
  • Uncontrolled prior lapatinib ditosylate therapy toxicity ≥ grade 2
  • Allergic reactions to IV contrast dye despite standard prophylaxis
  • History of malabsorption syndrome or disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism, or excretion of study drug
  • Conditions that would impair the patient's ability to swallow and retain oral medication
  • Concurrent disease or condition that would make the patient inappropriate for study participation or would interfere with the patient's safety
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol


  • Prior lapatinib ditosylate or trastuzumab allowed
  • At least 4 weeks since prior and no concurrent chemotherapy or investigational anticancer agents
  • At least 2 weeks since prior and no concurrent hormonal therapy
  • At least 2 weeks since prior and no concurrent lapatinib ditosylate prohibited medications, including CYP3A4 inhibitors or inducers, all herbal supplements, and gastric pH modifiers
  • More than 4 weeks since prior radiotherapy
  • No aspirin or plavix therapy within 7 days prior to tumor biopsy
  • No concurrent coumadin

    • Low molecular weight heparin allowed provided it can be held at least 24 hours prior to tumor biopsy
  • Concurrent gonadal suppression agents (i.e., Zoladex or Lupron) or palliative bisphosphonates (i.e., Zometa) allowed
  Contacts and Locations
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Please refer to this study by its identifier: NCT00544804

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Study Chair: Mark M. Moasser, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco Identifier: NCT00544804     History of Changes
Other Study ID Numbers: UCSF-077518
Study First Received: October 13, 2007
Last Updated: July 1, 2014

Keywords provided by University of California, San Francisco:
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
bone metastases

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2017