Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
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.
Timeline
- Start
- 2008-01
- Primary completion
- 2011-06
- Completion
- 2011-06
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lapatinib | Small molecule | 1000 mg | Oral |
| Subject | Lapatinib | Small molecule | 1250 mg | Oral |
| Subject | Lapatinib | Small molecule | 1500 mg | Oral |
| Subject | Temozolomide | Small molecule | 100 mg/m2 | Oral |
| Subject | Temozolomide | Small molecule | 150 mg/m2 | Oral |
| Subject | Temozolomide | Small molecule | 200 mg/m2 | Oral |