RATIONALE: CC-5013 may stop the growth of gliomas by stopping blood flow to the tumor.
PURPOSE: Phase I trial to study the effectiveness of CC-5013 in treating patients who have
- Determine the maximum tolerated dose of CC-5013 in patients with recurrent high-grade
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the antiangiogenic activity of this drug in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to concurrent
enzyme-inducing antiepileptic drugs (yes vs no).
Patients receive oral CC-5013 weekly for 3 weeks. Treatment repeats every 4 weeks for up to
12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of CC-5013 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3
or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at 2 weeks.
PROJECTED ACCRUAL: A maximum of 80 patients (40 per stratum) will be accrued for this study
within 20 months.
- One of the following:
- Histologically confirmed high-grade glioma
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Malignant glioma/astrocytoma, not otherwise specified
- Primitive neuroectodermal tumors
- Progressive glioma
- Clinically and radiographically diagnosed brain stem glioma
- Progressive or recurrent disease as determined by CT scan or MRI
- Biopsy allowed for prior recent (i.e., within the past 12 weeks) resection of
recurrent or progressive tumor
- Must have failed prior radiotherapy
- 18 and over
- Karnofsky 60-100%
- More than 8 weeks
- WBC at least 2,300/mm^3
- Platelet count at least 90,000/mm^3
- Hemoglobin at least 8 g/dL (transfusions allowed)
- Bilirubin less than 3 times upper limit of normal (ULN)
- SGOT less than 3 times ULN
- No significant active hepatic disease
- Creatinine less than 2.0 mg/dL OR
- Creatinine clearance at least 60 mL/min
- No significant active renal disease
- No significant active cardiac disease
- No other malignancy within the past 3 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix
- No significant active psychiatric disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since prior interferon
- No concurrent immunotherapy
- At least 6 weeks since prior nitrosoureas
- At least 4 weeks since prior temozolomide or carboplatin
- At least 3 weeks since prior procarbazine
- At least 2 weeks since prior vincristine
- At least 4 weeks since other prior cytotoxic chemotherapy
- No concurrent chemotherapy
- At least 2 weeks since prior tamoxifen
- Concurrent steroids allowed for control of the signs and symptoms of increased
intracranial pressure if on a stable dose for at least the past 5 days
- See Disease Characteristics
- At least 2 weeks since prior radiotherapy
- No concurrent radiotherapy
- See Disease Characteristics
- At least 2 weeks since prior tumor resection
- At least 2 weeks since other prior noncytotoxic agents
- Concurrent enzyme-inducing antiepileptic drugs allowed
- No concurrent rifampin
- No concurrent grapefruit juice
- No other concurrent investigational agents