Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer (LAPTEM)
September 18, 2012 updated by: Jules Bordet Institute
Phase 1 Study of the Combination of Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
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.
Study Overview
Status
Completed
Intervention / Treatment
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
Study Type
Interventional
Enrollment (Actual)
18
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Brussels, Belgium, 1000
- Jules Bordet Institute
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: I
Lapatinib plus 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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide
Time Frame: 18 months
|
18 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
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
|
18 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2008
Primary Completion (Actual)
June 1, 2011
Study Completion (Actual)
June 1, 2011
Study Registration Dates
First Submitted
February 1, 2008
First Submitted That Met QC Criteria
February 13, 2008
First Posted (Estimate)
February 14, 2008
Study Record Updates
Last Update Posted (Estimate)
September 19, 2012
Last Update Submitted That Met QC Criteria
September 18, 2012
Last Verified
June 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Breast Neoplasms
- Neoplasm Metastasis
- Brain Neoplasms
- Brain Diseases
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Protein Kinase Inhibitors
- Temozolomide
- Lapatinib
Other Study ID Numbers
- LAP111172
- EuDRACT 2007-005132-83
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.