Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer
Phase I: Patients will be treated in cohorts of 3-6 based on standard phase I dose
escalation parameters requiring 0/3 or 1/6 patients per cohort to have a DLT before dose
escalation. Dosing is as follows: Cohort 1-10 mg IT, cohort 2-20 mg IT, cohort 3-30 mg IT
and cohort 4-40 mg IT. Patients will be treated twice a week for 4 weeks, then once a week
for 4 weeks, and then every 2 weeks. Toxicity for DLT will be assessed during first 4 weeks
of treatment. Phase II: Patients will be treated with the MTD or maximal defined dose.
Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then
every 2 weeks.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the safety and maximum tolerated dose of IT trastuzumab.
The initial phase of this study will be a dose escalation trial of 3-6 patients per each dose level. Dose escalation will occur until the MTD or the maximal defined dose (MDD) (40 mg) is reached. The starting dose will be 10 mg for cohort 1, 20 mg for cohort 2, 30 mg for cohort 3 and 40 mg for cohort 4. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. The starting dose is based on the safety of this dose and higher doses as reported in the literature. The MTD or MDD will be used for phase II.
treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks
Jeffrey Raizer, MD
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Northwestern University||Chicago, Illinois 60611|