Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer

NCT ID: NCT00479856

Last Updated: 2012-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2010-03-31

Brief Summary

This study will evaluate the safety and efficacy of lapatinib in combination with chemotherapy (capecitabine, docetaxel, nab-paclitaxel) in subjects with ErbB2-overexpressing breast cancer whose disease has progressed during or within 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.

Conditions

Relapsed Breast Cancer; Neoplasms, Breast

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lapatinib plus Chemotherapy

Lapatinib is administered in combination with one of the following chemotherapies based on the discretion of the investigator : capecitabine, docetaxel or nab-paclitaxel.

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

Small molecule tyrosine kinase inhibitor

Capecitabine

Intervention Type: DRUG

Chemotherapy

Docetaxel

Intervention Type: DRUG

Chemotherapy

nab-Paclitaxel

Intervention Type: DRUG

Chemotherapy

Interventions

Lapatinib

Small molecule tyrosine kinase inhibitor

Intervention Type: DRUG

Capecitabine

Chemotherapy

Intervention Type: DRUG

Docetaxel

Chemotherapy

Intervention Type: DRUG

nab-Paclitaxel

Chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent.
• Histologically/cytologically confirmed breast cancer;

If the disease is restricted to a solitary lesion, the neoplastic nature of the lesion must be confirmed by cytology or histology.

• Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) [Therasse, 2000].
• Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by 3+ IHC in primary or metastatic tumor tissue.
• Subjects must have relapsed breast cancer where the disease progressed during or ≤ 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.

Note: Progression is defined using RECIST criteria, that is, either the appearance of new lesions or a >=20% increase in the sum of longest diameter (LD).

• Subjects must not have received prior anti-cancer therapy for metastatic breast cancer (MBC). Subjects who received prior antihormonal agents combined with trastuzumab for the treatment of disease which first presented as ER positive MBC and recurred while receiving trastuzumab or ≤ 3 months after completing this therapy are eligible.
• Subjects with stable central nervous system (CNS) metastases as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) are allowed. Treatment with prophylactic anticonvulsants is permitted, unless listed within the Prohibited Medications.
• Subjects must have a baseline cardiac ejection fraction (LVEF) ³50% measured by echocardiogram (ECHO) (or multigated acquisition (MUGA) scan if an ECHO cannot be performed). The same modality used at baseline must be used for repeat assessment throughout study. Only subjects with controlled or asymptomatic angina or arrhythmias are eligible.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
• Subjects must have archived tumor tissue from the initial diagnosis available for analysis. If tissue from the initial diagnosis is not available, then tissue must be obtained from a recurrent or metastatic site prior to initiating study treatment.
• Female ≥18 years.
• Subject must have adequate organ function as defined in Table 1.
• Table 1: Baseline Laboratory Values for Adequate Organ Function.

SYSTEM

Hematologic:

Absolute neutrophil count: ≥1.5 X 10^9/L

Hemoglobin: ≥9 g/dL

Platelets: ≥ 75 X 10^9/L

Hepatic:

AST, ALT and Alkaline phosphatase: ≤ 2.5 X ULN

Unless concomitant docetaxel, then ≤ 1.5 x ULN for AST and ALT, with AP ≤ 2.5 x ULN

Unless documented liver metastasis, then ≤ 5 x ULN

Serum bilirubin: ≤ 2.0 X ULN

Albumin: ≥ 2.5 g/dL

Renal:

Serum Creatinine: ≤ 1.5 mg/dL

• OR - Calculate Creatinine Clearance: ≥ 40 mL/min

1. Calculated by the Cockcroft and Gault Method [Cockcroft , 1976].

Exclusion Criteria

• Pregnant or lactating females.
• Women of childbearing potential who do not practice approved contraceptive methods (for example, intrauterine device [IUD], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.
• History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Concurrent therapy given to treat cancer (chemotherapy, radiation therapy, immunotherapy, biologic therapy, anti-hormonal therapy) while taking study medication.
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
• Malabsorption syndrome or resection of the stomach or small bowel significantly affecting gastrointestinal function.
• Have current active haptic or biliary disease (with excpetion of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
• Concurrent disease or condition that, in the opinion of the physician, would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (for example, uncontrolled infection, or any psychiatric condition prohibiting understanding or rendering of informed consent).
• Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents for anti-cancer therapy.
• Bisphosphonates may not be initiated after the first dose of study medication.
• Considered by the Investigator to have a life expectancy less than 3 months.
• Not able to swallow or retain oral medication.
• The subject with a known unmanageable hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to capecitabine, docetaxel, nab paclitaxel or their excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Hot Springs, Arkansas, United States

GSK Investigational Site

Anaheim, California, United States

GSK Investigational Site

Burbank, California, United States

GSK Investigational Site

Highland, California, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Hollywood, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Lawrenceville, Georgia, United States

GSK Investigational Site

Zion, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Metairie, Louisiana, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Tupelo, Mississippi, United States

GSK Investigational Site

Voorhees Township, New Jersey, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Sumter, South Carolina, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Ogden, Utah, United States

GSK Investigational Site

Abingdon, Virginia, United States

GSK Investigational Site

Fairfax, Virginia, United States

Countries

United States

Other Identifiers

EGF108916

Identifier Type: -

Identifier Source: org_study_id