Phase I Trial of a 5-day Regimen of Temodar Plus O6-Benzylguanine (O6-BG) in the Treatment of Patients With Recurrent / Progressive Glioblastoma Multiforme
1 primary objective is to determine maximum tolerated dose of Temodar in combo w
O6-benzylguanine administered for 5 consecutive days in pts w progressive/recurrent GBM.
Another primary objective is to characterize toxicity associated w Temozolomide in combo w
O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM. 3rd primary
objective is to determine Neulasta-supported MTD defined as MTD of Temozolomide in combo w
O6-BG administered for 5 days while receiving Neulasta once per treatment cycle between days
7 & 14 in pts w progressive/recurrent GBM. Secondary objective is to obtain preliminary
response rates of Temodar in combo w O6-BG administered for 5 consecutive days in pts w
progressive/recurrent GBM. Population is Glioblastoma. O6-BG Administration: O6-BG 120mg/m2
administered intravenously over 1 hr followed by continuous infusion of O6-BG at 30mg/m2/day
for 5 consecutive days. Every 48hrs repeat dose of 120mg/m2 over 1hr administered for total
of 3 doses.
Temodar Administration: Temodar administered orally, in fasting state within 60 mins of end
of 1st 1-hr infusion of O6-BG & then every 24 hrs during continuous infusion of O6-BG.
Temozolomide administered on day 1 of treatment cycle and every 24 hrs thereafter for 5 days
w treatment cycles repeated every 28 days. Body surface area calculated at beginning of each
cycle will be used to calculate daily dose of Temozolomide administered for that cycle.
Neulasta Administration. Neulasta administered by subcutaneous injection in 0.6mL
pre-filled syringe containing 6mg of pegfilgrastim. It will be administered once per
chemotherapy cycle between days 7 & 14. Neulasta should not be administered in period
between 14 days before & 24hrs after administration of cytotoxic chemo including
Data Analysis will be conducted by Biostatistics department of Duke.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicity
David A. Reardon, MD
Duke University Health System
United States: Food and Drug Administration
|Duke University Health System||Durham, North Carolina 27705|