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

July 1, 2014 updated by: University of California, San Francisco

A Phase I Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Study Type

Interventional

Enrollment (Actual)

41

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

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center

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

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

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 CONCURRENT THERAPY:

  • 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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lapatinib
Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
Genetic: gene expression analysis
Other: diagnostic laboratory biomarker analysis
Drug: lapatinib ditosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
estimated to be 12 months

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

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

August 1, 2007

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

October 13, 2007

First Submitted That Met QC Criteria

October 13, 2007

First Posted (Estimate)

October 16, 2007

Study Record Updates

Last Update Posted (Estimate)

July 2, 2014

Last Update Submitted That Met QC Criteria

July 1, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSF-077518

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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