talotrexin in treating patients with advanced or recurrent solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. purpose: this phase i trial is studying side effects, best way to give, and best dose of talotrexin in treating patients with advanced or recurrent solid tumors.

objectives: primary * determine the maximum tolerated dose of talotrexin in patients in patients with advanced or recurrent solid tumors. * determine the safety of this drug in these patients. * determine the dose-limiting toxic effects of this drug in these patients. secondary * determine the pharmacokinetics of this drug in these patients. * correlate pharmacokinetic parameters of this drug or patient characteristics with drug-related toxicity in these patients. * determine, preliminarily, the antitumor efficacy of this drug in these patients. outline: this is an open-label, dose-escalation, multicenter study. patients receive talotrexin iv over 5 minutes on day 1 or days 1 and 8 or days 1, 8, and 15. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cohorts of 1-6 patients receive escalating doses of talotrexin 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. an additional 6-10 patients are treated at the mtd. patients are followed at 1 month. projected accrual: a total of 20-40 patients will be accrued for this study within 9-12 months.

Eligibility criteria:
disease characteristics: * diagnosis of malignant solid tumor * metastatic or inoperable disease * no known curative or survival-prolonging palliative therapy exists or failed these prior therapies * no leukemia * no primary cns tumor * no third-space fluid collection (i.e., pleural effusion, ascites) * clinically insignificant small pleural or peritoneal effusions identified by ct scan, mri, or other diagnostic test allowed * no active\* brain metastases, including the following: * evidence of cerebral edema by ct scan or mri * progression since prior imaging study * requirement for steroids * clinical symptoms of/from brain metastases note: \*treated and/or stable brain metastasis allowed provided patient is asymptomatic patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 2 months hematopoietic * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * rbc folate ≥ lower limit of normal hepatic * bilirubin normal * sgot and sgpt ≤ 2.5 times upper limit of normal renal * creatinine clearance ≥ 50 ml/min other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no other uncontrolled serious medical or psychiatric illness prior concurrent therapy: biologic therapy * no prior bone marrow transplantation chemotherapy * more than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) endocrine therapy * see disease characteristics radiotherapy * more than 3 weeks since prior radiotherapy * no concurrent radiotherapy surgery * at least 3 weeks since prior surgery other * recovered from prior therapy * more than 3 weeks since prior antifolate therapy

Keywords: unspecified adult solid tumor, protocol specific