Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically proven high grade glioma that is progressive or recurrent following radiotherapy or chemotherapy.

• - Anaplastic astrocytoma.

• - Anaplastic oligodendroglioma.

• - Glioblastoma multiforme.

• - Prior low grade glioma that has progressed to high grade glioma following radiotherapy and/or chemotherapy allowed.

• - Measurable disease by MRI or CT scan.

PATIENT CHARACTERISTICS: Age:

• - 18 and over.

Performance status:

• - Karnofsky 60-100% Life expectancy: - Not specified.

Hematopoietic:

• - Absolute neutrophil count at least 1,500/mm^3.

• - Platelet count at least 100,000/mm^3.

Hepatic:

• - Bilirubin normal.

• - SGOT or SGPT no greater than 2.5 times upper limit of normal.

Renal:

• - Creatinine no greater than 1.5 mg/dL OR.

• - Creatinine clearance greater than 60 mL/min.

Cardiovascular:

• - No myocardial infarction, stroke, or congestive heart failure within the past 3 months.

Other:

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception during and for 1 month after study.

• - No serious active infection or medical illness that would preclude compliance.

• - HIV negative.

• - No history of gastrointestinal disorders that would interfere with absorption of study drug.

• - No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or breast, or basal cell or squamous cell skin cancer.

• - No hypersensitivity to tetracyclines or its derivatives.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - No concurrent filgrastim (G-CSF) Chemotherapy: - At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas) and recovered.

• - No more than 2 prior chemotherapy regimens.

Endocrine therapy:

• - Not specified.

Radiotherapy:

• - No prior large field radiotherapy (greater than 20% of total bone marrow) - At least 3 months since other prior radiotherapy and recovered.

Surgery:

• - No prior major upper gastrointestinal surgery.

• - At least 14 days since other prior major surgery.

Other:

• - No other concurrent investigational agents.

- No prolonged sun exposure

OBJECTIVES:

• - Determine the maximum tolerated dose, dose limiting toxicity, and safety profile of oral COL-3 alone or when combined with anticonvulsants known to be metabolized by CYP450 in patients with progressive or recurrent high grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme.

• - Define the pharmacokinetics and pharmacodynamics of COL-3 on this schedule and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics.

• - Determine the response rate, disease free survival, and survival in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study of COL-3. Patients are stratified by anticonvulsant (anticonvulsants that cause induction of CYP450 vs.#46;anticonvulsants that cause modest or no induction of CYP450 or no anticonvulsant).

• - Phase I: Patients receive oral COL-3 daily.

Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of COL-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.

• - Phase II: Patients receive oral COL-3 daily at the MTD from the phase I portion of this study.

Patients are followed every 2 months until death. PROJECTED ACCRUAL: A total of 15-18 patients will be accrued for phase I of the study and a total of 35 patients will be accrued for phase II of the study at a rate of 3 patients per month.