Lapatinib Resistance in Patients With Breast Cancer

Study of Resistance Mechanisms Against Lapatinib in Patients With ErbB-2-Positive Breast Cancers

RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about cancer and the development of drug resistance in patients.

PURPOSE: This research study is looking at lapatinib resistance in patients with breast cancer.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Other: laboratory biomarker analysis; Genetic: mutation analysis; Genetic: reverse transcriptase-polymerase chain reaction; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Drug: lapatinib ditosylate; Genetic: fluorescence in situ hybridization; Other: cell sorting

Detailed Description

OBJECTIVES:

• To identify secondary ErbB2 mutations in tumor tissue samples from patients with ErbB2-positive breast cancer treated with lapatinib ditosylate.
• To investigate ErbB2 copy number changes and expression levels.
• To determine abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance.

OUTLINE: Previously collected tumor tissue samples* are obtained for genetic analysis studies. Samples are analyzed for secondary ErbB2 mutations by nested PCR; ErbB2 copy number changes by quantitative PCR and standard histological FISH; and ErbB2 expression levels by quantitative RT-PCR and IHC. Patients also undergo blood sample collection for extraction of DNA (as normal control DNA) and isolation of EpCAM-positive circulating tumor cells using immunomagnetic cell separation technology. Additional research studies may include mutational and amplification analysis of the c-MET and PI3K pathways.

NOTE: *Patients may undergo biopsy if a post-treatment tumor tissue sample is unavailable.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44024
      • Geauga Regional Hospital
    • Cleveland, Ohio, United States, 44060
      • Lake/University Ireland Cancer Center
    • Cleveland, Ohio, United States, 44121
      • University Suburban Health Center
    • Cleveland, Ohio, United States, 44122
      • UHHS Chagrin Highlands Medical Center
    • Cleveland, Ohio, United States, 44130
      • Southwest General Health Center
    • Cleveland, Ohio, United States, 44145
      • UHHS Westlake Medical Center
    • Cleveland, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Primary care clinic

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed invasive breast cancer

  • ErbB2-positive disease

• Has received or is currently receiving lapatinib ditosylate

  • Documented clinical benefit while receiving lapatinib ditosylate (e.g., stable disease of ≥ 12 weeks duration OR a radiographic response)
• Must have tumor tissue samples available for research studies
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• Not pregnant*
• Coagulation profile normal*
• Platelet count > 100,000/mm³* NOTE: *For patients requiring a post-treatment biopsy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent chemotherapy or trastuzumab (Herceptin®) allowed
• No concurrent anticoagulants, including warfarin or low-molecular weight heparin*
• No concurrent antiplatelet therapy, including aspirin, clopidogrel, or other antiplatelet agents* NOTE: *For patients requiring a post-treatment biopsy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Secondary ErbB2 mutations
ErbB2 copy number changes and expression levels
Abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Balazs Halmos, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): October 2, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: CASE15107 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); CASE-15107-CC488