Clinical trial NCT00614978: Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Brain Metastases
HER2 Positive
Keywords: HER-2 positive; brain metastases
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Schering-Plough
First posted: 2008-02-14
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide
timeFrame: 18 months
Secondary outcomes:
measure: 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
timeFrame: 18 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Jules Bordet Institute
Study officials:
affiliation: Jules Bordet Institute
name: Evandro de Azambuja, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: