Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or
progressive primary malignant glioma treated with or without concurrent enzyme-inducing
anticonvulsant drugs.
- Determine whether this drug has sufficient activity to warrant further development in
these patients. (phase II)
Secondary
- Determine the qualitative and quantitative toxic effects of this drug in these
patients.
- Determine the pharmacokinetic behaviors of this drug in these patients.
- Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of
this drug in these patients.
- Determine the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified
according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no).
- Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gimatecan 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.
- Phase II: Patients receive gimatecan as in phase I at the MTD. Patients are followed
for at least 1 month and then every 2 months thereafter.
PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I [15-21 per stratum] and
21-41 for phase II) will be accrued for this study within 24 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic
astrocytoma, or anaplastic oligodendroglioma)
- Recurrent or progressive primary CNS neoplasm by contrast-enhanced MRI
- Tumor progression after prior surgery, radiotherapy, or chemotherapy
- Measurable or evaluable disease
- Failed prior standard curative or palliative therapy (phase I only)
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- At least 3 months
Hematopoietic
- Absolute neutrophil count ≥ 2,000/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- SGPT and SGOT ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver
metastases are present)
- Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
- Bilirubin normal
Renal
- Creatinine ≤ 1.5 times ULN
Cardiovascular
- No myocardial infarction with the past year
- No heart failure (including cardiac insufficiency controlled by digitalis and
diuretics)
- No irreversible arrhythmias requiring permanent medication
- No uncontrolled hypertension
Gastrointestinal
- No gastrointestinal dysfunction that would alter absorption or motility, such as any
of the following:
- Active peptic ulcer
- Inflammatory bowel disease
- Known intolerance to lactose
- Malabsorption syndromes
- Intestinal sub-occlusion
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No active infection
- No mentally incapacitated patients
- No other concurrent severe disease that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent immunotherapy
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- No more than 1 prior chemotherapy regimen
- No other concurrent chemotherapy
Endocrine therapy
- Concurrent corticosteroids allowed if dose stable for the past 2 weeks
- No concurrent hormonal therapy
Radiotherapy
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
- At least 3 weeks since prior surgical resection
- No prior gastrointestinal surgery that would affect drug absorption
Other
- More than 4 weeks since prior participation in any other investigational drug study
- More than 72 hours since prior systemic antibiotics
- No concurrent H2 antagonists, antacids, or proton pump inhibitors
- If any of these therapies are necessary, ≥ 3 hours must elapse after gimatecan
administration
- No other concurrent anticancer therapy
- No other concurrent investigational drugs
- No other concurrent immunosuppressive agents
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Timothy F. Cloughesy, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000372874
NCT ID:
NCT00087061
Start Date:
May 2004
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult anaplastic oligodendroglioma
- recurrent adult brain tumor
- adult glioblastoma
- adult anaplastic astrocytoma
- adult giant cell glioblastoma
- adult gliosarcoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Glioma
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
