Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
Condition: Metastatic Breast Cancer; Brain Metastases; HER2 Positive
MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Brain Diseases
Study type: Interventional
Phase: Phase 1

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
    

Intervention name(s): lapatinib and temozolomide
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Tykerb
Intervention MeSH terms: Temozolomide; Lapatinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HER-2 positive; brain metastases