Chemotherapy in Treating Patients With Advanced or Metastatic Solid Tumors

OBJECTIVES: I. Determine the intolerable dose level of intoplicine in patients with locally
advanced or metastatic cancer. II. Determine recommended phase II dose of intoplicine in
these patients. III. Determine the principal and dose limiting toxicities of intoplicine in
these patients, and determine the duration and reversibility of the toxicities. IV. Determine
the magnitude of plasma concentrations that are achieved and maintained on this regimen and
relate this parameter to toxicity outcome and antitumor activity. V. Determine preliminary
evidence of antitumor activity of intoplicine in these patients.

OUTLINE: This is a dose escalation study. The first 3 patients receive intoplicine IV by
continuous infusion for 5 days. Treatment is repeated every 28 days in the absence of disease
progression or unacceptable toxicity. Subsequent cohorts of 3-6 patients receive escalating
doses of intoplicine, first by increasing the number of days that the drug is infused to 10,
15, and 21, then by increasing the dosage and keeping the infusion time constant at 21 days.
The intolerable dose level is defined as the lowest dose at which at least 2 of 3 or 6
patients experience dose limiting toxicity during course 1 or 2.

PROJECTED ACCRUAL: A total of 20-35 patients will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically or cytologically proven solid tumor refractory to
conventional cytotoxic anticancer therapy or for which no curative therapy exists
Measurable or evaluable disease No active, progressive brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: SWOG 0-2 Life expectancy: At
least 12 weeks Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at
least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL
SGOT/SGPT no greater than 3 times upper limit of normal No nonmalignant hepatic disease
Renal: Creatinine no greater than 2.0 mg/dL Potassium and magnesium at least lower limit of
normal (LLN) Calcium at least LLN Cardiovascular: QTc interval on echocardiogram less than
450 milliseconds No myocardial infarction within past 6 months No uncontrolled congestive
heart failure No unstable angina No active cardiomyopathy No unstable ventricular
arrhythmia No uncontrolled hypertension Other: Not pregnant or nursing Fertile patients
must use effective contraception Must have functional central venous access device or
percutaneous intravenous catheter No known hypersensitivity to intoplicine or its analogs
No active alcoholism or drug addiction No uncontrolled, unstable psychotic disorders No
serious infections No underlying medical conditions that may be aggravated by treatment

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks
since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No other
concurrent antineoplastic therapy Endocrine therapy: Not specified Radiotherapy: At least 3
weeks since prior radiotherapy (except short courses (no greater than 5 fractions) of
nonmyelosuppressive, palliative radiotherapy) and recovered No concurrent radiotherapy
Surgery: Not specified Other: At least 3 weeks since prior investigational therapy No other
concurrent investigational therapy