Irinotecan Plus ICI D1694 in Treating Patients With Advanced Solid Tumors

OBJECTIVES: I. Determine the maximum tolerated dose of ICI D1694 (TDX) when given with
irinotecan (CPT-11) every 3 weeks in patients with advanced solid malignancies. II. Describe
the pharmacokinetics of TDX and CPT-11 when given in combination. III. Investigate the
relationship between topoisomerase I expression in peripheral mononuclear cells and
myelosuppression and/or gastrointestinal toxicity. IV. Investigate the effect of CPT-11 on
thymidylate synthase expression in tumor.

OUTLINE: This is a dose-escalating study to determine the maximum tolerated dose (MTD) of ICI
D1694 (TDX) given in combination with irinotecan. Irinotecan is given intravenously on day 1
and ICI D1694 intravenously on day 2. Treatment is repeated every 3 weeks until disease
progression or unacceptable toxicity intervenes. Cohorts of 3-6 patients receive escalated
doses of TDX until the MTD is defined; an additional 10-12 patients will be entered at the
MTD to confirm this as a recommended phase II dose.

PROJECTED ACCRUAL: 30-35 patients will be entered.

DISEASE CHARACTERISTICS: Histologically confirmed solid tumor for which no effective
therapy exists Measurable or evaluable disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0 or 1 Hematopoietic:
WBC at least 3,000 AGC at least 1,500 Platelets at least 100,000 Hepatic: Bilirubin no
greater than 1.5 mg/dL AST/ALT no greater than 5 times normal Renal: Creatinine no greater
than 1.5 mg/dL Metabolic: Glucose no greater than 200 mg/dL Electrolytes within 10% normal
Other: No active infection that contraindicates entry No significant medical problem that
contraindicates entry Effective contraception required of fertile patients Able and willing
to participate in pharmacokinetic sampling

PRIOR CONCURRENT THERAPY: At least 3 weeks since chemotherapy (6 weeks since mitomycin or
nitrosoureas) and recovered At least 3 weeks since radiotherapy and recovered