Phase I Study of Patupilone and RAD001

Inclusion Criteria:

• All patients must have malignancy refractory to standard therapy or for whom no standard, effective therapy is available.
• Patient must have performance status 0-2 on the ECOG Performance Status (see Appendix B)
• Patient's disease must be measurable (RECIST) or evaluable (e.g., cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions which do not fulfill RECIST criteria for measurable disease).
• Patients must have intact intestinal absorption
• Patients must have adequate organ function
• Patient must have recovered from toxicity of prior chemotherapy and/or radiotherapy. Patient may not have received chemotherapy in the prior 4 weeks. Patients may have not received radiotherapy in the prior 3 weeks.
• Patient (male or female) must be ≥ 18 years old.
• Women must not be pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study, and for three months following discontinuation of study drug.
• Signed written informed consent.

Exclusion Criteria:

• Patient has received greater than 3 prior cytotoxic regimens for metastatic disease.
• Prior therapy with epothilones, rapamycin, rapamycin analogs, or known sensitivity to these agents
• Prior treatment with any investigational drug within the preceding 4 weeks.
• Patient has history of bone marrow or stem cell transplant.
• Patient has received prior radiation therapy to greater than 25% of the bone marrow.
• Patients has newly diagnosed, not yet treated or uncontrolled brain metastases or leptomeningeal disease.
• Patient has known hypersensitivity to the components of study drugs or its analogs.
• Patient with known Grade 3 or 4 hypersensitivity to macrolide antibiotics (eg. clarithromycin, erythromycin, azithromycin).
• Patient with any active (acute or chronic) or uncontrolled infection requiring systemic therapy.
• Patients with chronic treatment with systemic steroids or another immunosuppressive agent
• Patient with known HIV infection.
• Patients with unresolved diarrhea within the last 7 days prior to start of treatment.
• Concomitant treatment with medications that are listed as clinically relevant inducers or inhibitors of cytochrome P450 (CYP3A).
• Patients taking Coumadin® or other agents containing warfarin, with the exception of low dose Coumadin® (1 mg or less) administered prophylactically for maintenance of in-dwelling lines or ports
• Herbal preparations or related over-the-counter preparations containing herbal ingredients (eg. St. John's Wort)
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, or severely impaired lung function
• Any patient with uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
• Any patient with nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• Patients receiving immunization with attenuated live vaccines during study participation.