Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer (LAPTEM)

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Schering-Plough
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT00614978
First received: February 1, 2008
Last updated: September 18, 2012
Last verified: June 2011
  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 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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 ]

Enrollment: 18
Study Start Date: January 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
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.
Other Name: Tykerb

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614978

Locations
Belgium
Jules Bordet Institute
Brussels, Belgium, 1000
Sponsors and Collaborators
Jules Bordet Institute
GlaxoSmithKline
Schering-Plough
Investigators
Principal Investigator: Evandro de Azambuja, MD, PhD Jules Bordet Institute
  More Information

No publications provided

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT00614978     History of Changes
Other Study ID Numbers: LAP111172, EuDRACT 2007-005132-83
Study First Received: February 1, 2008
Last Updated: September 18, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

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

Additional relevant MeSH terms:
Brain Diseases
Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Central Nervous System Diseases
Nervous System Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Temozolomide
Dacarbazine
Lapatinib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014