Lapatinib Resistance in Patients With Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00898573
• Other study ID #: CASE15107
• Secondary ID: P30CA043703CASE1
• Status: Withdrawn
• Phase: Phase 1
• First received: May 9, 2009
• Last updated: October 1, 2015
• Start date: July 2008

Study information

• Verified date: October 2015
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• lapatinib ditosylate

Genetic:
• fluorescence in situ hybridization

• gene expression analysis

• mutation analysis

• polymerase chain reaction

• reverse transcriptase-polymerase chain reaction

Other:
• cell sorting

• immunohistochemistry staining method

• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Geauga Regional Hospital	Cleveland	Ohio
United States	Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Lake/University Ireland Cancer Center	Cleveland	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Cleveland	Ohio
United States	Southwest General Health Center	Cleveland	Ohio
United States	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio
United States	UHHS Westlake Medical Center	Cleveland	Ohio
United States	University Suburban Health Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Secondary ErbB2 mutations			No
Primary	ErbB2 copy number changes and expression levels			No
Primary	Abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance			No