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Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer (LAPTEM)
This study is currently recruiting participants.
Verified by Jules Bordet Institute, May 2008
Sponsors and Collaborators: Jules Bordet Institute
GlaxoSmithKline
Schering-Plough
Information provided by: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT00614978
  Purpose

Objectives:

Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomideSecondary - Obtain preliminary information on the clinical anti-tumor activity of lapatinib plus temozolomide on brain metastases secondary to HER-2 positive breast cancer including Objective Response Rate (ORR), Clinical Benefit (CB) and Duration of Response (DR)

Methodology:

Phase I, single-centre, open-label, dose-escalation study of combining lapatinib and temozolomide in HER-2 positive breast cancer patients with progressive brain metastases after surgery or radiotherapy or radiosurgery

Treatment:

Temozolomide will be given orally for 5 days of every 28 days, at doses of either 100mg/m2/day or 150mg/m2/day or 200mg/m2/day AND Lapatinib will be given orally every day at either 1000mg/day or 1250mg/day or 1500mg/day.Sequential cohorts will be escalated in increments according to the dose escalation scheme, and determined by dose limiting toxicities.


Condition Intervention Phase
Metastatic Breast Cancer
Brain Metastases
HER2 Positive
 Drug: lapatinib and temozolomide
 Phase I

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Brain Diseases Breast Cancer Cancer
Drug Information available for: Temozolomide Lapatinib Lapatinib Ditosylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title: Phase 1 Study of the Combination of Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer

Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Obtain preliminary information on the clinical anti-tumor activity of lapatinib plus temozolomide on brain metastases secondary to HER-2 positive breast cancer including Objective Response Rate, Clinical Benefit and Duration of Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: January 2008
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
I: Experimental
Lapatinib plus temozolomide
Drug: lapatinib and temozolomide
Temozolomide will be given orally for 5 days of every 28 days, at doses of either 100mg/m2/day or 150mg/m2/day or 200mg/m2/day AND Lapatinib will be given orally every day at either 1000mg/day or 1250mg/day or 1500mg/day.

Detailed Description:

Patients selection criteria:

  • age 18 - 70 years
  • Women with cytologically or histologically proven metastatic breast cancer with recurrent / progressive brain metastases evaluable by MRI, after standard treatment with surgery (at least 3 weeks prior) or WBRT (at least 3 weeks prior) or stereotactic RT (at least 1 week prior); or otherwise deemed as unsuitable for standard treatment in the first instance
  • Known HER-2 positive status (immunohistochemistry (IHC) 3+ Fluorescence In Situ Hybridization (FISH) positive )
  • Previous chemotherapy (adjuvant and metastatic regimens) allowed
  • Previous treatment with trastuzumab allowed (Trastuzumab to be discontinued prior to study entry)
  • At least one measurable lesion in the brain, defined as any lesion >5mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
  • Expected life-expectancy of more than 3 months
  • ECOG performance status of 0, 1 or 2
  • Adequate bone marrow, renal and hepatic functionsLVEF
  • LVEF 50% measured by echocardiography or MUGA scan
  • Concomitant corticosteroids and anti-convulsants for symptomatic brain metastases are allowed
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 - 70 years
  • Women with cytologically or histologically proven metastatic breast cancer with recurrent / progressive brain metastases evaluable by MRI, after standard treatment with surgery (at least 3 weeks prior) or WBRT (at least 3 weeks prior) or stereotactic RT (at least 1 week prior); or otherwise deemed as unsuitable for standard treatment in the first instance
  • Known HER-2 positive status (immunohistochemistry (IHC) 3+ Fluorescence In Situ Hybridization (FISH) positive )
  • Previous chemotherapy (adjuvant and metastatic regimens) allowed
  • Previous treatment with trastuzumab allowed (Trastuzumab to be discontinued prior to study entry)
  • At least one measurable lesion in the brain, defined as any lesion >5mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
  • Expected life-expectancy of more than 3 months
  • ECOG performance status of 0, 1 or 2
  • Adequate bone marrow, renal and hepatic functionsLVEF
  • LVEF >50% measured by echocardiography or MUGA scan
  • Concomitant corticosteroids and anti-convulsants for symptomatic brain metastases are allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00614978

Contacts
Contact: Evandro de Azambuja, MD, PhD +3225417244 evandro.azambuja@bordet.be
Contact: Ahmad Awada, MD,PhD +3225413189 ahmad.awada@bordet.be

Locations
Belgium
Jules Bordet Institute Recruiting
Brussels, Belgium, 1000
Contact: Evandro de Azambuja, MD, PhD     +3225417244     evandro.azambuja@bordet.be    
Contact: Alfino Buttice     +3225417262     alfino.buttice@bordet.be    
Principal Investigator: Evandro de Azambuja, MD, PhD            
Principal Investigator: Ahmad Awada, MD, PhD            
Sponsors and Collaborators
Jules Bordet Institute
GlaxoSmithKline
Schering-Plough
Investigators
Principal Investigator: Evandro de Azambuja, MD, PhD Jules Bordet Institute
  More Information

Responsible Party: Jules Bordet Institute ( Jules Bordet Institute )
Study ID Numbers: LAP111172, EuDRACT 2007-005132-83
Study First Received: February 1, 2008
Last Updated: May 5, 2008
ClinicalTrials.gov Identifier: NCT00614978  
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Jules Bordet Institute:
HER-2 positive; brain metastases

Study placed in the following topic categories:
Brain Neoplasms
Skin Diseases
Neoplasm Metastasis
Central Nervous System Diseases
Breast Neoplasms
Lapatinib
 Central Nervous System Neoplasms
Brain Diseases
Temozolomide
Nervous System Neoplasms
Breast Diseases

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
 Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009



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