Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

Neoplasms, Breast Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00263588
• Other study ID #: EGF105084
• Secondary ID: CLAP016A22022005
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2005
• Est. completion date: March 15, 2018

Study information

• Verified date: November 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: March 15, 2018
• Est. primary completion date: September 25, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasm Metastasis
• Neoplasms, Breast

Intervention

Drug:
• lapatinib
tyrosine kinase inhibitor

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Herston	Queensland
Australia	Novartis Investigative Site	North Sydney	New South Wales
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	Ringwood East	Victoria
Australia	Novartis Investigative Site	South Brisbane	Queensland
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Bruxelles
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Weston	Ontario
France	Novartis Investigative Site	Dijon Cedex
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris Cedex 05
France	Novartis Investigative Site	Toulouse cedex
Germany	Novartis Investigative Site	Frankfurt am Main	Hessen
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Greece	Novartis Investigative Site	Neo Faliro
India	Novartis Investigative Site	Bangalore
India	Novartis Investigative Site	Mumbai
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Perugia	Umbria
Italy	Novartis Investigative Site	Reggio Emilia	Emilia-Romagna
Japan	Novartis Investigative Site	Aichi
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Geneve
Switzerland	Novartis Investigative Site	Locarno
Taiwan	Novartis Investigative Site	Tainan County
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Brighton
United Kingdom	Novartis Investigative Site	Manchester	Lancashire
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Santa Fe	New Mexico
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sioux City	Iowa
United States	Novartis Investigative Site	Tyler	Texas
United States	Novartis Investigative Site	Vallejo	California
United States	Novartis Investigative Site	Washington	District of Columbia
United States	Novartis Investigative Site	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Greece,  India,  Italy,  Japan,  Poland,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (1)

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, includin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants With Central Nervous System (CNS) Best Overall Response	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	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Primary	The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)	Summary of CNS Objective Response (the Complete Response + Partial Response)	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Percentage of Participants With Improvement in Neurological Signs and Symptoms (NSS) Measured Using the Neurological Examination Worksheet	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.	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Percentage of Subjects With a CNS Objective Response or Improvement in Baseline Neurological Signs and Symptoms (NSS)	Summary of Proportion of Subjects with a CNS Objective Response or Improvement in Baseline NSS	baseline and weeks 8, 16, 24, 32, 40, 48
Secondary	Duration of Central Nervous System (CNS) Objective Response	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.	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Percentage of Patients With CNS Disease Control (Complete Response, Partial Response or Stable Disease) at 6 Months of Lapatinib Therapy	The CNS disease control rate, defined as the percentage of subjects with CR, PR or stable disease at Week 24	from Start of lapatinib to 6 months
Secondary	Time to Progression (TTP) at Any Site	Summary of Kaplan-Meier Estimates for Progression Free Survival at Any Site	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Overall Survival (OS)	Overall survival (OS) defined as the time from initiation of investigational product to death due to any cause.	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Summary of Site of First Progression	baseline to time of disease progression or death	time from baseline to data cutoff (25 Sept 2007); approximately 2 years
Secondary	Primary Cause of Death	Summary of Overall All-cause mortality (Main Study and Extension)	time from baseline to data cutoff (25 Sept 2007); approximately 2 years