Clinical trial NCT00898573: Lapatinib Resistance in Patients With Breast Cancer
Official title: Study of Resistance Mechanisms Against Lapatinib in Patients With ErbB-2-Positive Breast Cancers
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Primary care clinic

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Secondary ErbB2 mutations
measure: ErbB2 copy number changes and expression levels
measure: Abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Geauga Regional Hospital
state: Ohio
city: Cleveland
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Suburban Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Chagrin Highlands Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Southwest General Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Westlake Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Thomas Budd, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
name: Balazs Halmos, MD
role: PRINCIPAL_INVESTIGATOR
References: