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Completed

NCT Number: NCT00263588

Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

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.

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Key information

Conditions

Neoplasms, Breast Brain Diseases Brain Neoplasms Breast Diseases Breast Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, North Sydney, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed Informed Consent
  • ErbB2(HER2)overexpressing breast cancer.
  • Brain lesion(s) which are progressing.
  • Prior treatment of brain metastases with Whole Brain Radiotherapy (WBR)and/or Stereotactic Radiosurgery (SRS).
  • Prior treatment with trastuzumab (Herceptin), either alone or in combination with chemotherapy.
  • Cardiac ejection fraction(LVEF)within the institutional range of normal as measured by Echocardiogram.
  • Able to swallow an oral medication.
  • Adequate kidney and liver function.
  • Adequate bone marrow function.

Exclusion criteria

  • Pregnant or lactating females.
  • Conditions that would effect the absorption of an oral drug.
  • History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents.
  • Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel.
  • Serious medical or psychiatric disorder that would interfere with the patient's safety or informed consent.

Treatment and study plan

Lapatinib

Drug

tyrosine kinase inhibitor

Primary outcomes

  1. The Number of Participants With Central Nervous System (CNS) Best Overall Response

    Time frame: 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

  2. The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)

    Time frame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years

    Summary of CNS Objective Response (the Complete Response + Partial Response)

Secondary outcomes

  1. Percentage of Participants With Improvement in Neurological Signs and Symptoms (NSS) Measured Using the Neurological Examination Worksheet

    Time frame: 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.

  2. Percentage of Subjects With a CNS Objective Response or Improvement in Baseline Neurological Signs and Symptoms (NSS)

    Time frame: baseline and weeks 8, 16, 24, 32, 40, 48

    Summary of Proportion of Subjects with a CNS Objective Response or Improvement in Baseline NSS

  3. Duration of Central Nervous System (CNS) Objective Response

    Time frame: 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.

  4. Percentage of Patients With CNS Disease Control (Complete Response, Partial Response or Stable Disease) at 6 Months of Lapatinib Therapy

    Time frame: 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

  5. Time to Progression (TTP) at Any Site

    Time frame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years

    Summary of Kaplan-Meier Estimates for Progression Free Survival at Any Site

  6. Overall Survival (OS)

    Time frame: 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.

  7. Summary of Site of First Progression

    Time frame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years

    baseline to time of disease progression or death

  8. Primary Cause of Death

    Time frame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years

    Summary of Overall All-cause mortality (Main Study and Extension)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase II Study of Lapatinib for Brain Metastases in Subjects With ErbB2-Positive Breast Cancer Following Trastuzumab-based Systemic Therapy and Cranial Radiotherapy

Important dates

Study start
2005
Primary completion
2007
Study completion
2018
First posted
Dec 9, 2005
Registry last updated
Dec 12, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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