Phase I Study of MK-1775 with Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma and Evaluation of Intratumoral Drug Distribution in Patients with Recurrent Glioblastoma
This study is for newly diagnosed patients. The purpose of this cohort is to obtain more safety data for MK-1775 given concurrently with RT+TMZ and with adjuvant TMZ. 12 patients will be enrolled and treated at the MTD established in Arm 1 during the initial 10-week cycle of MK-1775+RT+TMZ+4 weeks rest, and then at the MTD established in Arm 2 during 28-day maintenance cycles of MK-1775+adjuvant TMZ.
Patients must be 18 years of age or older. Patients must have a Karnofsky Performance Status ï?³ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others). Absolute neutrophil count greater than 1,500/mcL Platelets greater than 100,000/mcL Hemoglobin greater than 9 g/dL Total bilirubin within normal institutional limits AST (SGOT)/ALT (SGPT)3 Ã? institutional upper limit of normal Creatinine within normal institutional limits APTTâ?¤ 1.5 x institutional upper limit of normal Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with prior malignancies must be disease-free for five years. Patients must be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment. Patients must be able to swallow whole capsules
Phase I Arm 1 â?? Initiation Cycle (10 Weeks) (Newly diagnosed GBM) Weeks 1-6: RT, M-F Weeks 1-6: MK-1775, starting dose 100 mg MWF Weeks 1-6: TMZ, daily 75 mg/m2 Weeks 7-10: Rest, no treatment Arm 1 â?? Maintenance Cycles 1-6 (4 weeks each) TMZ: Days 1-5 (150-200 mg/m2), repeated q 28 days Phase I Arm 2 â?? 4-Week Cycles x 6 (Newly diagnosed GBM) Cycle 1 Days 1-5: TMZ 150 mg/m2 Days 1-5: MK-1775, starting dose 100 mg Days 1, 3, 5 Cycles 2+ Days 1-5: TMZ 200 mg/m2 Days 1-5: MK-1775, same dose as Cycle 1
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