A Phase I and Pharmacokinetic Study of SR-45023A Administered Once Every 7 Days

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed locally advanced or
metastatic solid tumors refractory to standard therapy or for which no standard therapy
exists (surgery, radiotherapy, and/or chemotherapy) Measurable or evaluable disease by
medical photograph, plain x-ray, CT, MRI, palpation, or serum tumor markers at least 2
times upper limit of normal No symptomatic, progressive brain metastases by CT or MRI scan
No cerebral edema No leukemia or multiple myeloma

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: SWOG 0-2 Life expectancy: At
least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hemoglobin at least 9.0 g/dL No coagulation disorders Hepatic:
Bilirubin normal AST and ALT no greater than 3 times upper limit of normal (ULN) (no
greater than 5 times ULN if liver involvement) PT or INR, and PTT normal Renal: Creatinine
no greater than 1.5 mg/dL Cardiovascular: No cardiac conduction abnormalities Other: Not
pregnant or nursing Negative pregnancy test Fertile patients must use effective
contraception No active or uncontrolled infection No other concurrent severe disease No
known hypersensitivity to SR-45023A analogs No concurrent or recent (within past 6 months)
small bowel obstruction, symptoms of small bowel obstruction, or any other
gastrointestinal disease impacting absorption of study drug No psychiatric disorders or
geographic distance that would prevent compliance

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: See
Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks since
carboplatin, mitomycin, or nitrosoureas) and recovered No prior SR-45023A No other
concurrent chemotherapy Endocrine therapy: No concurrent steroid therapy for brain disease
No concurrent hormonal cancer therapy (except contraception, hormone replacement therapy,
or corticosteroids) Radiotherapy: See Disease Characteristics At least 4 weeks since prior
radiotherapy and recovered No concurrent radiotherapy (except symptomatic radiotherapy for
pathologic fractures) Surgery: At least 4 weeks since prior surgery and recovered Other:
At least 4 weeks since prior investigational agents No other concurrent investigational
agents No concurrent anticoagulation therapy (e.g., heparin) except low dose warfarin for
central venous catheter patency No concurrent digoxin, beta blockers, or calcium channel
blockers No concurrent H2 histamine inhibitors (e.g., ranitidine, famotidine, or
cimetidine), proton pump inhibitors (e.g., omeprazole or lansoprazole), or other drugs
that might interfere with study drug absorption