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

NCT00614978 | Completed Phase 1

• 2 other identifiers: LAP111172EuDRACT 2007-005132-83
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer; Brain Metastases; HER2 Positive

Keywords

HER-2 positive; brain metastases

Outcome Measures

Primary Outcomes (1)

• Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide

  18 months

Secondary Outcomes (1)

• 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

Study Arms (1)

I

EXPERIMENTAL

Lapatinib plus temozolomide

Drug: lapatinib and temozolomide

Interventions

lapatinib and temozolomide DRUG

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.

Also known as: Tykerb

I

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• Jules Bordet Institute: lead
• GlaxoSmithKline: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Jules Bordet Institute

Brussels, 1000, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Lapatinib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Evandro de Azambuja, MD, PhD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2008
• First Posted: February 14, 2008
• Study Start: January 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 19, 2012

Record last verified: 2011-06

Locations

BE (1)