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

Free University of Brussels (ULB)

Status and phase

Completed

Phase 1

Conditions

Brain Metastases

HER2 Positive

Metastatic Breast Cancer

Treatments

Drug: lapatinib and temozolomide

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00614978

EuDRACT 2007-005132-83

LAP111172

Details and patient eligibility

About

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.

Full 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

Enrollment

18 patients

Sex

Female

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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