cc-8490 in treating patients with recurrent or refractory high-grade gliomas

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy, such as cc-8490, work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i trial to study the effectiveness of cc-8490 in treating patients who have recurrent or refractory high-grade gliomas.

objectives: primary * determine the maximum tolerated dose of cc-8490 in patients with recurrent or refractory high-grade gliomas. * determine, preliminarily, the toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. secondary * determine, preliminarily, the potential anti-glioma activity of this drug in these patients. outline: this is a dose-escalation study. patients receive oral cc-8490 once daily on days 1 and 3-28 (course 1 only). beginning with course 2 and for all subsequent courses, patients receive oral cc-8490 once daily on days 1-28. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of cc-8490 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. once the mtd is determined, a total of 10 patients are treated at that dose. patients are followed within 2 weeks. projected accrual: a total of 34 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed supratentorial malignant glioma, including any of the following: * glioblastoma multiforme * gliosarcoma * anaplastic astrocytoma * anaplastic oligodendroglioma * anaplastic mixed oligoastrocytoma * malignant glioma/astrocytoma not otherwise specified or * clinical and radiographic diagnosis of progressive low-grade glioma * radiographically diagnosed infiltrating brain stem gliomas not amenable to biopsy allowed * recurrent or progressive disease as determined by 1 of the following: * ct scan or mri within the past 21 days * biopsy within the past 12 weeks * failed prior radiotherapy patient characteristics: age * 18 and over performance status * karnofsky 60-100% life expectancy * more than 8 weeks hematopoietic * granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 (transfusion independent) * hemoglobin at least 8 g/dl (transfusion allowed) hepatic * bilirubin no greater than 1.5 mg/dl * ast and alt no greater than 2 times upper limit of normal * no significant active hepatic disease that would preclude study participation renal * creatinine no greater than 1.5 mg/dl or * creatinine clearance at least 60 ml/min * no significant active renal disease that would preclude study participation cardiovascular * no significant active cardiac disease that would preclude study participation other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 2 months after study participation * no other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no significant active psychiatric disease that would preclude study participation * no other condition or laboratory abnormality that would preclude study participation * able to swallow capsules whole prior concurrent therapy: biologic therapy * at least 2 weeks since prior interferon * no concurrent immunotherapy chemotherapy * at least 2 weeks since prior vincristine * at least 3 weeks since prior procarbazine * at least 4 weeks since prior temozolomide or carboplatin * at least 6 weeks since prior nitrosoureas * no other concurrent anticancer chemotherapy endocrine therapy * at least 2 weeks since prior tamoxifen * concurrent steroids allowed provided dose has been stable for at least 5 days prior to study enrollment radiotherapy * see disease characteristics * at least 2 weeks since prior radiotherapy * no concurrent radiotherapy surgery * at least 2 weeks since prior resection of a recurrent or progressive tumor other * at least 2 weeks since other prior non-cytotoxic therapy * at least 4 weeks since other prior cytotoxic therapies * more than 28 days since prior experimental study drugs * no other concurrent investigational agents

Keywords: adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult glioblastoma adult mixed glioma adult brain stem glioma recurrent adult brain tumor adult giant cell glioblastoma adult gliosarcoma