Lapatinib in Treating Patients With Advanced or Metastatic Breast Cancer That Overexpresses HER2
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
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
San Francisco, California, United States, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
|
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
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCSF-077518
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