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

NCT ID: NCT00614978

Last Updated: 2012-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2011-06-30

Brief Summary

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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

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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

Conditions

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Metastatic Breast Cancer Brain Metastases HER2 Positive

Keywords

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HER-2 positive; brain metastases

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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I

Lapatinib plus temozolomide

Group Type EXPERIMENTAL

lapatinib and temozolomide

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Tykerb

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Schering-Plough

INDUSTRY

Sponsor Role collaborator

Jules Bordet Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evandro de Azambuja, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Jules Bordet Institute

Locations

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Jules Bordet Institute

Brussels, , Belgium

Site Status

Countries

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Belgium

Other Identifiers

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EuDRACT 2007-005132-83

Identifier Type: -

Identifier Source: secondary_id

LAP111172

Identifier Type: -

Identifier Source: org_study_id