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

Sponsor

Jules Bordet Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00614978

Collaborator

GlaxoSmithKline (Industry), Schering-Plough (Industry)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer Brain Metastases HER2 Positive	Drug: lapatinib and temozolomide	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Tykerb

Arm

Intervention/Treatment

Experimental: I

Lapatinib plus temozolomide

Drug: lapatinib and temozolomide

Other Names:

Tykerb

Outcome Measures

Primary Outcome Measures

Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide [18 months]

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 [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts 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