Clinical trial NCT00263588: Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Breast
Keywords: breast cancer
brain metastases
ErbB2 positive
HER2 positive
neoplasms
cancer
lapatinib
LAP016A2202
LAP016A
CLAP016A2202
GW572016
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-12-09
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants With Central Nervous System (CNS) Best Overall Response
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary outcomes:
measure: Percentage of Participants With Improvement in Neurological Signs and Symptoms (NSS) Measured Using the Neurological Examination Worksheet
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: Percentage of Subjects With a CNS Objective Response or Improvement in Baseline Neurological Signs and Symptoms (NSS)
timeFrame: baseline and weeks 8, 16, 24, 32, 40, 48
measure: Duration of Central Nervous System (CNS) Objective Response
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: Percentage of Patients With CNS Disease Control (Complete Response, Partial Response or Stable Disease) at 6 Months of Lapatinib Therapy
timeFrame: from Start of lapatinib to 6 months
measure: Time to Progression (TTP) at Any Site
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: Overall Survival (OS)
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: Summary of Site of First Progression
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
measure: Primary Cause of Death
timeFrame: time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Vallejo
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Washington
country: United States
facility: Novartis Investigative Site
state: District of Columbia
city: Boca Raton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Sioux City
country: United States
facility: Novartis Investigative Site
state: Iowa
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Albuquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Albuquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Albuquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Santa Fe
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tyler
country: United States
facility: Novartis Investigative Site
state: Texas
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Yakima
country: United States
facility: Novartis Investigative Site
state: Washington
city: North Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Box Hill
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Ringwood East
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Perth
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Adelaide
country: Australia
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Weston
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Dijon Cedex
country: France
facility: Novartis Investigative Site
city: Paris Cedex 05
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse cedex
country: France
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Neo Faliro
country: Greece
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
city: Mumbai
country: India
facility: Novartis Investigative Site
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: Umbria
city: Aichi
country: Japan
facility: Novartis Investigative Site
city: Saitama
country: Japan
facility: Novartis Investigative Site
city: Saitama
country: Japan
facility: Novartis Investigative Site
city: Tokyo
country: Japan
facility: Novartis Investigative Site
city: Tokyo
country: Japan
facility: Novartis Investigative Site
city: Tokyo
country: Japan
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: Locarno
country: Switzerland
facility: Novartis Investigative Site
city: Tainan County
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
state: Lancashire
city: Brighton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Sutherland S, Ashley S, Miles D, Chan S, Wardley A, Davidson N, Bhatti R, Shehata M, Nouras H, Camburn T, Johnston SR. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases--the UK experience. Br J Cancer. 2010 Mar 16;102(6):995-1002. doi: 10.1038/sj.bjc.6605586. Epub 2010 Feb 23.