Study of Oral AP23573 to Treat Patients With Refractory or Advanced Malignancies

Inclusion Criteria:

• Male or female patients ≥18 years of age.
• Patients with a histological/cytological diagnosis of unresectable or metastatic cancer that is refractory to standard therapies or for which no standard therapy exists.
• Patients must must have measurable or nonmeasurable lesions assessable using an appropriate radiographical procedure (e.g., CT or MRI scans).
• Fertile male or female patients who agree to use approved barrier methods of contraception (non hormonal methods).
• ECOG performance status ≤ 2.
• Adequate renal and hepatic function, defined as: *Total serum bilirubin ≤ 2 x upper limit of normal (ULN) for the institution; *AST and/or ALT ≤ 2.5 x ULN for the institution (≤ 5 x if due to hepatic metastases); *Serum albumin ≥ 2 g/dL; Serum creatinine ≤ 2 x ULN for the institution
• Adequate bone marrow function, defined as: * ANC ≥ 1.5 x 10^9/L; *Platelet count ≥ 100 x 10^9/L
• Serum cholesterol < 350 mg/dL and triglycerides < 400 mg/dL.
• Anticipated life expectancy of ≥ 3 months.
• Able to give and understand a written informed consent.

Exclusion Criteria:

• Patients with active central nervous system (CNS) metastases or leptomeningeal disease, not controlled by prior surgery or radiotherapy.
• Prior therapy with rapamycin, rapamycin analogs or tacrolimus, or known sensitivity to these agents.
• Prior anticancer treatment, standard or experimental, within 4 weeks prior to the first dose of AP23573 (except LH-RH agonists); the interval is ≥ 2 weeks for signal transduction inhibitors with a half-life known to be < 24 hours, and is ≥ 6 weeks for nitrosourea or mitomycin.
• Concomitant treatment with medications that induce, inhibit, or are metabolized by cytochrome P450 (CYP3A). Patients should be off these medications 2 weeks prior to the first dose of AP23573.
• Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by National Cancer Institute (NCI) Terminology Criteria and alopecia).
• Another primary malignancy within the past three years (except in situ carcinoma).
• Known or suspected hypersensitivity to any excipient contained in the study drug.
• Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).
• Significant uncontrolled cardiovascular disease.
• Active infection requiring systemic therapy.
• Women who are pregnant or lactating.
• Known HIV infection .
• Other life-threatening illness, any medical condition, or organ system dysfunction, which, in the opinion of the Investigator and Sponsor, would either compromise the patient's safety or interfere with evaluation of the safety of AP23573, or could interfere with the absorption of the oral study drug.
• Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug.
• Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within the last 3 to 4 weeks prior to the first dose of AP23573.