A Phase I/II, Open-Label, Non-Randomized, Multicenter, Single Agent Study Of Intravenous SDX-102 For The Treatment Of Patients With MTAP-Deficient High Grade Recurrent Malignant Gliomas
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I/II, Open-Label, Non-Randomized, Multicenter, Single Agent Study Of Intravenous SDX-102 For The Treatment Of Patients With MTAP-Deficient High Grade Recurrent Malignant Gliomas
OBJECTIVES:
- Determine the maximum tolerated dose of alanosine (SDX-102) with or without
enzyme-inducible antiepileptic drugs (EIAEDs) in patients with methylthioadenosine
phosphorylase (MTAP)-deficient high-grade progressive or recurrent malignant gliomas.
- Determine the pharmacokinetics of this drug administered concurrently with EIAEDs in
these patients.
OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study. Patients
are stratified according to concurrent anticonvulsant drug use (drugs that induce hepatic
metabolic enzymes vs drugs that cause modest or no induction of hepatic metabolic enzymes OR
no anticonvulsant drug).
Patients receive alanosine (SDX-102) IV continuously for 5 days. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SDX-102 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.
After completion of study therapy, patients are followed at 1 week and then every 2 months
thereafter.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant glioma of 1 of the following types:
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
- Progressive or recurrent disease after prior radiotherapy with or without
chemotherapy
- Low-grade glioma that progressed after prior radiotherapy with or without
chemotherapy and is found to be high-grade glioma after biopsy allowed
- No more than 2 prior treatment regimens
- Measurable disease by CT scan or MRI
- Documented absence of methylthioadenosine phosphorylase (MTAP) on fixed tumor
specimens
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- Transaminases ≤ 4 times upper limit of normal
Renal
- Creatinine ≤ 1.5 mg/dL
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception before, during, and for 4
weeks after study participation
- Mini mental state exam score of ≥ 15
- No psychological or sociological condition, addictive disorder, or family problem
that would preclude study compliance
- No other malignancy within the past 5 years except curatively treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix or breast
- No concurrent serious infection or medical illness that would preclude study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim
[GM-CSF])
Chemotherapy
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
Endocrine therapy
- Must be maintained on a stable or lower corticosteroid regimen from the time of the
baseline scan until the start of study treatment
- No concurrent steroids as antiemetics
Radiotherapy
- See Disease Characteristics
- At least 3 months since prior radiotherapy
Surgery
- Not specified
Other
- Recovered from prior therapy
- More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic
enzymes
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Surasak Phuphanich, MD, FAAN
Investigator Role:
Study Chair
Investigator Affiliation:
Winship Cancer Institute of Emory University
Authority:
United States: Federal Government
Study ID:
CDR0000349473
NCT ID:
NCT00075894
Start Date:
March 2004
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult anaplastic oligodendroglioma
- adult anaplastic astrocytoma
- adult glioblastoma
- recurrent adult brain tumor
- adult giant cell glioblastoma
- adult gliosarcoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Glioma
Name | Location |
|---|---|
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit, Michigan 48202 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa, Florida 33612 |
