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

Primary Purpose

Metastatic Breast Cancer, Brain Metastases, HER2 Positive

Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
lapatinib and temozolomide
Sponsored by
Jules Bordet Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring HER-2 positive; brain metastases

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Jules Bordet Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

I

Arm Description

Lapatinib plus temozolomide

Outcomes

Primary Outcome Measures

Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide

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

Full Information

First Posted
February 1, 2008
Last Updated
September 18, 2012
Sponsor
Jules Bordet Institute
Collaborators
GlaxoSmithKline, Schering-Plough
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1. Study Identification

Unique Protocol Identification Number
NCT00614978
Brief Title
Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
Acronym
LAPTEM
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute
Collaborators
GlaxoSmithKline, Schering-Plough

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Brain Metastases, HER2 Positive
Keywords
HER-2 positive; brain metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
I
Arm Type
Experimental
Arm Description
Lapatinib plus temozolomide
Intervention Type
Drug
Intervention Name(s)
lapatinib and temozolomide
Other Intervention Name(s)
Tykerb
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide
Time Frame
18 months
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evandro de Azambuja, MD, PhD
Organizational Affiliation
Jules Bordet Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jules Bordet Institute
City
Brussels
ZIP/Postal Code
1000
Country
Belgium

12. IPD Sharing Statement

Learn more about this trial

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

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