Sirolimus and Vorinostat in Advanced Cancer

Inclusion Criteria:

1. Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
2. There is no limit on the number of prior treatment regimens
3. Patients must be off prior cytotoxic chemotherapy for at least three weeks. For biologic or targeted therapy, there should be five half lives or three weeks, whichever is shorter, between their last treatment and the first dose on this trial.
4. Patients may receive palliative radiation therapy before or during treatment on protocol, provided that there is measurable or evaluable disease out of the radiation field. Patients may receive palliative radiation therapy, if needed, 48 hours after last dose of investigational drug. In addition patients may be enrolled on trial seven days following palliative radiation. We will closely monitor for the appearance of radiation recall reactions. Hormonal therapy may continue in patients who have been on such treatment for three months or longer.
5. ECOG performance status 0-3
6. Patients must have adequate organ and marrow function as defined by: absolute neutrophil count >/= 1000uL, platelets >/= 50,000uL, bilirubin </=2mg/dL in the absence of Gilbert's syndrome, ALT </= 2 x ULN or </=5x ULN if liver metastases present, creatinine </= 2mg/dL
7. As the effect of sirolimus and vorinostat in combination on the developing human fetus is not known, women of child-bearing potential and men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 3 months after completion
8. Female patients with child-bearing potential must have a negative serum or urine pregnancy test within 7 days of study enrollment. Nursing mothers should discontinue nursing
9. Ability to understand and the willingness to sign a written informed consent document
10. Measurable or evaluable disease
11. Patient must be able to swallow pills

Exclusion Criteria:

1. Myocardial infarction within 3 months prior to starting treatment
2. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital or St. Johns wort, cyclosporine, diltiazem, ketoconazole should be discontinued if possible
3. Patient has a known hypersensitivity to the components of study drugs, its analogues, or drugs of similar chemical or biologic composition
4. Patient is pregnant or breastfeeding
5. Major surgical procedure within 28 days of day 1 of therapy
6. Use of any other concurrent investigational agents or anticancer agents except for hormonal therapy as outlined in inclusion criteria