Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

Phase 2

Completed

Conditions: Neoplasms, Breast

Interventions: Drug: lapatinib

Registration Number: NCT00263588

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: Determine how safe and effective lapatinib is when used to treat patients with ErbB2 overexpressing breast cancer that has spread to the brain and is still progressing there even after radiation treatment using WBRT (whole brain radiotherapy) or SRS (stereotactic radiosurgery) to the brain. Lapatinib is an oral drug that will be taken every day. Tests for safety and efficacy will be performed every 4 weeks or 8 weeks (depending on the test) during the course of the study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 242

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
single arm	lapatinib	750 mg lapatinib administered orally twice daily

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Central Nervous System (CNS) Best Overall Response	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Summary of CNS Objective Response (Lapatinib Monotherapy - MITT Population) Response to lapatinib in patients with progressive brain metastases from ErbB2-overexpressing breast cancer. The primary indicator of drug efficacy was CNS objective response rate. A CNS objective response was defined as either a Complete response (CR) or Partial response (PR), as assessed by volumetric analysis of brain Magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of Neurological signs and symptoms (NSS) A CNS objective response rate was defined as a 50% volumetric reduction in sum of CNS target lesions, with no new or progressive CNS or non-CNS lesions, no increases in tumor-related steroid requirements and no worsening of neurological signs or symptoms
The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Summary of CNS Objective Response (the Complete Response + Partial Response)

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Improvement in Neurological Signs and Symptoms (NSS) Measured Using the Neurological Examination Worksheet	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Physician-reported NSS worksheet is derived from 13 AEs and measured by NCI CTCAE v3.0 grouped into 7 categories: level of consciousness, neurological symptoms, cranial nerves, language, strength, sensation, \& ataxia. Improvement of NSS required: Decrease by 1 or more grades from baseline of any tumor-related NSS, with confirmation at least 4 wks later, No development or worsening in any tumor-related NSS during interval, No radiographic evidence of CNS progression (assessed by volumetric MRI) or systemic (non-CNS) progression (assessed by RECIST) during interval, Stable or decreasing steroids during interval as defined by GSK equivalent doses of an alternative corticosteroid or a dose increase for non-tumor related reasons didn't constitute a steroid increase. Improvement in any non-tumor associated NSS didn't constitute improvement in NSS. Neurological exam, using Neurological Examination Worksheet was assessed at baseline \& each 4 wks. Categories below are not mutually exclusive.
Summary of Site of First Progression	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	baseline to time of disease progression or death
Time to Progression (TTP) at Any Site	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Summary of Kaplan-Meier Estimates for Progression Free Survival at Any Site
Overall Survival (OS)	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Overall survival (OS) defined as the time from initiation of investigational product to death due to any cause.
Percentage of Subjects With a CNS Objective Response or Improvement in Baseline Neurological Signs and Symptoms (NSS)	baseline and weeks 8, 16, 24, 32, 40, 48	Summary of Proportion of Subjects with a CNS Objective Response or Improvement in Baseline NSS
Percentage of Patients With CNS Disease Control (Complete Response, Partial Response or Stable Disease) at 6 Months of Lapatinib Therapy	from Start of lapatinib to 6 months	The CNS disease control rate, defined as the percentage of subjects with CR, PR or stable disease at Week 24
Primary Cause of Death	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	Summary of Overall All-cause mortality (Main Study and Extension)
Duration of Central Nervous System (CNS) Objective Response	time from baseline to data cutoff (25 Sept 2007); approximately 2 years	The duration of CNS objective response, defined as the time from first CNS Objective response until tumor progression at any site or death due to any cause. A CNS objective response was defined as either a Complete Response (CR) or Partial Response (PR), as assessed by volumetric analysis of magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of tumor-related neurological signs or symptoms.