AG2037 in Treating Patients With Advanced, Metastatic, or Recurrent Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxic effects of AG2037 in patients with advanced, metastatic, or recurrent solid tumor.
• Determine the safety and tolerance of this drug in these patients.
• Assess the pharmacokinetics of this drug in these patients.
• Document any antitumor effects of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive AG2037 IV weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AG2037 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 4 weeks.

PROJECTED ACCRUAL: A total of 18-60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor

• Advanced, metastatic, or recurrent disease
• No curative therapy exists
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL (unless due to Gilbert's syndrome)
• SGOT OR SGPT no greater than 2 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

Other:

• No unstable or severe concurrent medical condition that would preclude study participation
• No sociological or familial condition that would preclude study compliance
• No psychological or addictive disorder that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 40% of bone marrow

Surgery:

• Not specified

Other:

• At least 2 weeks since prior blood transfusions
• At least 4 weeks since prior investigational agent and recovered
• No prior glycinamide ribonucleotide formyltransferase (GARFT) inhibitor
• No concurrent extradietary folate supplements
• No concurrent allopurinol
• No other concurrent anticancer or investigational agents