RATIONALE: Drugs used in chemotherapy, such as KRN5500, work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of KRN5500 in treating patients who have solid tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxic effects of KRN5500 in patients with solid tumors.
• Assess the safety of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the response, by 3'deoxy- 3'fluorothymidine positron emission tomography scan, of a subset of patients treated with this drug.

Secondary

• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Determine pharmacodynamic relationships for the pharmacological effect of this drug upon surrogate markers of activity and toxicity in these patients.
• Compare the toxicity profiles for the 1-hour and 72-hour infusion administration schedules of this drug in these patients.

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

Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion durations. After the longest duration of infusion time is safely reached, cohorts of 3-6 patients receive escalating doses of KRN5500 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, additional patients are accrued to receive treatment with KRN5500 at the recommended phase II dose.

Patients are followed every 4 weeks until resolution of all toxicity.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.

DISEASE CHARACTERISTICS:

• Metastatic or inoperable malignancy for which there is no known curative or survival-prolonging palliative therapy or that has failed all such therapies

  • No leukemia or primary CNS tumors

• No active brain metastases, including:

  • No evidence of cerebral edema by CT scan or MRI
  • No progression from prior imaging study
  • No requirement for steroids
  • No related clinical symptoms

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No uncontrolled or significant cardiac disease
• No myocardial infarction within the past 6 months
• No significant congestive heart failure
• No prior clinically significant atrial or ventricular arrhythmia
• No prior second- or third-degree heart block
• No evidence of acute ischemia or prolonged QTc interval (greater than 450 ms) on electrocardiogram

Pulmonary:

• No uncontrolled or significant pulmonary disease

Other:

• No serious uncontrolled medical disorder that would preclude study participation
• No active infection
• No psychiatric illness 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 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since prior major surgery