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
18 Years
N/A
Both
Glioblastoma, Gliosarcoma
Trial Information
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
Temozolomide.
Data Analysis will be conducted by Biostatistics department of Duke.
Inclusion Criteria:
- Pts have histologically proven supratentorial GBM
- Pts have recurrent/progressive MG. If pt received stereotactic radiosurgery /
brachytherapy as part of their prior therapy, then histologic confirmation of
recurrence/metabolic imaging consistent w recurrent tumor is recommended but not
mandated
- There must be measurable disease on contrast-enhanced magnetic resonance imaging
study / CT scan performed <2wks of study drug administration
- Interval of >12 wks between completion of XRT & enrollment on protocol
- Interval of >4 wks between prior chemo & enrollment on protocol unless there is
unequivocal evidence of tumor progression
- Interval of >2 wks between prior surgical resection & enrollment on protocol unless
there is unequivocal evidence of tumor progression
- Age >18 yrs
- KPS >70 percent
- Following baseline study will be required <1wk of study drug administration: serum
creatinine < 1.5 x ULN & Hematologic Status
- Following baseline studies will be required <1wk of study drug administration:
absolute neutrophil count >2000 cells/microliter; platelet count >125,000
cells/microliter
- Following baseline studies will be required <1 wk of study drug administration: serum
SGOT & total bilirubin < 2.5 x ULN
- Signed informed consent, approved by IRB, will be obtained prior to initiating
treatment
- Pts w Reproductive Potential: Pts must agree to practice effective birth control
measures while on study & for 2 months after completing therapy
Exclusion Criteria:
- Pregnant/breast feeding women/ women/men w reproductive potential not practicing
adequate contraception. Therapy may be associated w potential toxicity to fetus/child
that exceeds mini risks necessary to meet health needs of mother
- Prior treatment w O6-BG + Temozolomide in combo
- Active infection requiring intravenous antibiotics
- Known diagnosis of HIV infection
- Pts w history of another primary malignancy that is currently clinically
significant/currently requires active intervention
- Pts unwilling/unable to comply w protocol due to serious medical/psychiatric
condition
- Pts who have received investigational drugs <2 wks prior to start on study drug/have
not recovered from side effects of such therapy.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose limiting toxicity
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
David A. Reardon, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Duke University Health System
Authority:
United States: Food and Drug Administration
Study ID:
Pro00004058
NCT ID:
NCT00612989
Start Date:
February 2005
Completion Date:
July 2008
Related Keywords:
- Glioblastoma
- Gliosarcoma
- Glioblastoma
- Gliosarcoma
- GBM
- Temodar
- Temozolomide
- O6-BG
- O6-Benzylguanine
- Recurrent GBM
- Progressive GBM
- Brain tumor
- Malignant glioma
- Neulasta
- Pegfilgrastim
- Glioblastoma
- Gliosarcoma
Name | Location |
|---|---|
| Duke University Health System | Durham, North Carolina 27705 |
