Sirolimus or Vorinostat and Hydroxychloroquine in Advanced Cancer

The goal of this clinical research study is to find the highest tolerable dose of sirolimus or vorinostat that can be given in combination with hydroxychloroquine to patients with advanced cancer. The safety of these drug combinations will also be studied.

Study Drug Dose Level:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of hydroxychloroquine and either sirolimus or vorinostat, based on when you joined this study, availability of spots for each drug combination, and what your doctor thinks is in your best interest. Up to 11 dose levels of the sirolimus and hydroxychloroquine combination and 7 dose levels of the vorinostat and hydroxychloroquine combination will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of the study drug combination. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of each drug combination is found.

Once the highest tolerated dose of each drug combination is found, up to 28 more participants (14 per combination) will be given this dose. The study doctor will decide which drug combination each participant is given, based on their tumor type.

Study Drug Administration:

Each study "cycle" is 21 days.

You will take hydroxychloroquine and either vorinostat or sirolimus by mouth, 1 time a day, every day. You should take the pills at about the same time each day with food and a cup (8 ounces) of water.

Study Visits:

At every study visit, you will be asked about any health conditions you have, drugs you may be taking, and if you have had any side effects.

Weekly During Cycle 1:

° Blood (about 2 teaspoons) will be drawn for routine tests.

At the beginning of each cycle beginning with 2:

* You will have a physical exam.
* Your medical history will be recorded.
* You will be asked if you have any muscle weakness or difficulty while moving.

Every 6 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT to check the status of the disease. If the study doctor thinks it is needed, they will be performed more often. If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

About every 3 months, you will have an eye exam.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

This is an investigational study. Sirolimus is FDA approved and commercially available for the treatment of patients with a kidney transplant. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. Hydroxychloroquine is FDA approved and commercially available to treat malaria. The use of these drugs combinations is investigational.

Up to 224 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility Criteria:
Inclusion Criteria:

1. Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
2. Patients must be \>/= 18 years.
3. Patients must be \>/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be \>/= 5 half-lives or \>/= 3 weeks form the last dose (whichever comes first).
4. ECOG performance status \</= 2
5. Patients must have adequate organ and marrow function defined as: absolute neutrophil count \>/= 1,000/mL;platelets \>/=50,000/mL; creatinine \</= 2 X ULN; total bilirubin \</= 2.0 (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); ALT(SGPT) \</= 5 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; ALT(SGPT) \</= 8 X ULN;cholesterol \</= 350 mg/dL; triglycerides \</= 400 mg/dL (sirolimus and hydroxychloroquine only).
6. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
7. Patients must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

1. Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
2. Pregnant or lactating women.
3. History of hypersensitivity to sirolimus.
4. History of hypersensitivity to vorinostat
5. History of hypersensitivity to hydroxychloroquine
6. History of hypersensitivity to any component of the formulation.
7. Patients unwilling or unable to sign informed consent document.
8. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
9. Patients with known glucose-6-phosphate dehydrogenase deficiency.
10. Patients with porphyria cutanea tarda.
11. Patients with psoriasis.
12. Patients with pre-existing maculopathy or retinopathy of the eye.
13. Patients who have a pre-existing myopathy.