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

Phase 1

Completed

• Conditions: Metastatic Breast Cancer; Brain Metastases; HER2 Positive
• Interventions: Drug: lapatinib and temozolomide

• Registration Number: NCT00614978
• Lead Sponsor: Jules Bordet Institute

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.

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 Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-02-01
• Study First Submitted QC: 2008-02-13
• Study First Posted: 2008-02-14
• Status Verified: 2011-06
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Last Update Submitted: 2012-09-18
• Last Update Posted: 2012-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 18

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
I	lapatinib and temozolomide	Lapatinib plus temozolomide

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Jules Bordet Institute; 🇧🇪 Brussels, Belgium