Phase I Study of PN401, Fluorouracil, Leucovorin and CPT-11 in Patients With Solid Tumors

Inclusion Criteria

• Must be at least 18 years of age;
• Life expectancy: At least 3 months;
• Performance status: ECOG of 0 or 1;
• Histologic or cytologic proof of a solid tumor cancer that is not amenable to curative surgical resection;
• Evaluable or measurable disease documented within 4 weeks of the start of treatment;
• Prior chemotherapy or radiotherapy is allowed if 4 weeks or more have elapsed prior to starting treatment and patients have recovered from toxicities of prior treatment;
• Adequate organ function:

Hematopoietic: ANC = 1500/ul or more, Platelets = 100,000/ul or more, Hemoglobin = 9.5 g/dL or more, transfusion prior to evaluation is allowed; Hepatic: Bilirubin = 2.0 mg/dL or less and SGPT(ALT) and SGOT(AST) < 3 x upper limit of normal (< 5 x upper limit of normal if liver metastases present) Renal: Serum Creatinine < 2.0 mg/dL;

• Patient has the initiative, geographic proximity, and means to be compliant with the protocol;
• Fertile patients (male or female) must agree to use effective contraception;
• Must be able to swallow and retain tablets.

Exclusion Criteria

• Major surgery within the four weeks preceding the start of treatment;
• Serious medical or psychiatric illness that would prevent self-determined informed consent;
• Intensive chemotherapy treatment;
• Infection or antibiotics at the time of screening;
• Uncontrolled cardiovascular, pulmonary, renal, neurologic, psychiatric, or hepatic dysfunction;
• Pregnant or nursing;
• Pre-existing diarrhea or uncontrolled clinically significant illness other than cancer (i.e. ulcerative colitis, malabsorption syndrome);
• Brain metastases that have not been stable for more than 3 months;
• Known Dihydropyrimidine Dehydrogenase (DPD) deficiency.