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

Metastatic Breast Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00614978
• Other study ID #: LAP111172
• Secondary ID: EuDRACT 2007-005
• Status: Completed
• Phase: Phase 1
• First received: February 1, 2008
• Last updated: September 18, 2012
• Start date: January 2008
• Est. completion date: June 2011

Study information

• Verified date: June 2011
• Source: Jules Bordet Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Brain Metastases
• Breast Neoplasms
• HER2 Positive
• Metastatic Breast Cancer

Intervention

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.

Locations

Country	Name	City	State
Belgium	Jules Bordet Institute	Brussels

Sponsors (3)

Lead Sponsor	Collaborator
Jules Bordet Institute	GlaxoSmithKline, Schering-Plough

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide		18 months	Yes
Secondary	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	No