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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00544804
Recruitment Status : Completed
First Posted : October 16, 2007
Last Update Posted : July 2, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE October 13, 2007
First Posted Date  ICMJE October 16, 2007
Last Update Posted Date July 2, 2014
Study Start Date  ICMJE August 2007
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2013)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2007)
Maximum tolerated dose
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lapatinib in Treating Patients With Advanced or Metastatic Breast Cancer That Overexpresses HER2
Official Title  ICMJE A Phase I Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Metastatic Cancer
Intervention  ICMJE
  • Drug: lapatinib ditosylate
  • Genetic: gene expression analysis
  • Other: diagnostic laboratory biomarker analysis
Study Arms  ICMJE Experimental: Lapatinib
Dose Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy With Biomarker Analysis in Patients With HER2-Overexpressing Breast Cancer
Interventions:
  • Drug: lapatinib ditosylate
  • Genetic: gene expression analysis
  • Other: diagnostic laboratory biomarker analysis
Publications * Chien AJ, Munster PN, Melisko ME, Rugo HS, Park JW, Goga A, Auerback G, Khanafshar E, Ordovas K, Koch KM, Moasser MM. Phase I dose-escalation study of 5-day intermittent oral lapatinib therapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer. J Clin Oncol. 2014 May 10;32(14):1472-9. doi: 10.1200/JCO.2013.52.1161. Epub 2014 Apr 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 1, 2014)
41
Original Enrollment  ICMJE
 (submitted: October 13, 2007)
15
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00544804
Other Study ID Numbers  ICMJE UCSF-077518
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Mark M. Moasser, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP