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.
- 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.
- 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
Patients are followed at 1 month.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12
- Diagnosis of malignant solid tumor
- Metastatic or inoperable disease
- No known curative or survival-prolonging palliative therapy exists OR failed these
- 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
- 18 and over
- ECOG 0-2
- At least 2 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- RBC folate ≥ lower limit of normal
- Bilirubin normal
- SGOT and SGPT ≤ 2.5 times upper limit of normal
- Creatinine clearance ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other uncontrolled serious medical or psychiatric illness
PRIOR CONCURRENT THERAPY:
- No prior bone marrow transplantation
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- See Disease Characteristics
- More than 3 weeks since prior radiotherapy
- No concurrent radiotherapy
- At least 3 weeks since prior surgery
- Recovered from prior therapy
- More than 3 weeks since prior antifolate therapy