Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer

Phase 2

Completed

• Conditions: Neoplasms, Breast
• Interventions: Drug: lapatinib

• Registration Number: NCT00105950
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer. Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry). Treatment will consist of daily oral therapy with lapatinib. A patient may continue treatment as long as they are receiving benefit. Blood samples for hematology and chemistry panels, MUGA/ECHO (multigated acquisition/echocardiogram) exams and physical exams will be performed throughout the study to monitor safety.

Detailed Description

This Phase II open label, multicenter study is designed to evaluate the efficacy, safety, and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to patients with relapsed or refractory inflammatory breast cancer. Eligible patients must have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor that is readily accessible for biopsy, and must have previously received treatment with an anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients). Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of ErbB1. The primary objective for this study is to evaluate the objective response rate (defined as complete response plus partial response). Secondary objectives are to evaluate clinical benefit including quality of life parameters, progression-free survival, overall survival, time-to-response, response duration, safety and tolerability, pharmacodynamic effects on intracellular mediators that regulate tumor cell growth and survival, as well as effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and ErbB2 in peripheral blood.

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2005-03-18
• Study First Submitted QC: 2005-03-18
• Study First Posted: 2005-03-21
• Primary Completion: 2007-09
• Study Completion: 2010-05
• Status Verified: 2015-05
• Last Update Submitted: 2015-09-24
• Last Update Posted: 2015-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lapatinib	lapatinib	Single arm study of lapatinib with no comparator arm.

Primary Outcome Measures

Name	Time	Method
Objective Response rate (complete response plus partial response)	Week 84

Secondary Outcome Measures

Name	Time	Method
Comparison of the effects of lapatinib on biomarkers that are involved in regulating tumor cell proliferation and survival (e.g., phosphorylated forms of Erk1/2 and Akt, STAT3, S6 Kinase, Bad, truncated ErbB2 and potentially other downstream mediators of	Day 28
Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months	week 84
Calculation of progression-free survival, defined as the time between the first dose of investigational product and the first documented sign of disease progression or death.	week 84
Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR.	week 84
Evaluation of adverse events (AEs), changes in laboratory values and echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) results from pre-dose, during dosing and post-dose assessments	week 84
tumor cell growth and survival) by quantitative IHC and by direct and genome-wide methods (e.g., direct sequencing and DNA microarray) in tumor tissue collected prior to and following 28 days of lapatinib monotherapy.	Day 28
Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment.	week 84
Examination of the effects of lapatinib therapy on the levels of circulating ErbB1 and ErbB2 ECD and the proteomic profile of peripheral blood. Investigation of the use of FDG-PET to predict early response to treatment with lapatinib.	Day 28
Clinical benefit (progression free survival, time to progression, response duration)	week 84
Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression.	week 84

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 London, United Kingdom