Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

Study Drug Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of vorinostat and either sirolimus, everolimus, or temsirolimus based on when you
joined this study. Up to 9 dose levels of sirolimus and vorinostat will be tested. Up to 3
dose levels of everolimus and vorinostat will be tested. Up to 3 dose levels of temsirolimus
and vorinostat will be tested. Three (3) to 9 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
the combination vorinostat and sirolimus, everolimus, or temsirolimus is found.

Once the highest tolerated dose of the combinations are found, up to 14 participants with the
tumor type that is most likely to respond to the study drug combinations will receive the
study drugs at that dose level.

Study Drug Administration:

Each study "cycle" is 28 days.

There are 3 arms in this study, Arm A, Arm B, and Arm C. You will be assigned to an arm
depending on when you enroll in the study and what your doctor thinks you will benefit from.
You will take vorinostat either with sirolimus (Arm A), with everolimus (Arm B), or with
temsirolimus (Arm C).

Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same
time each day with food and a cup (8 ounces) of water.

If you are in Arm A, on Day 7 of Cycle 1, you will start taking vorinostat by mouth 1 time a
day. You should take it at about the same time each day with food and a cup (8 ounces) of
water.

If your are in Arm B, you will take everolimus by mouth at the same time every day with or
without food, swallowed whole with a glass (8 ounces) of water. Do not chew, break, or crush
everolimus.

If you are in Arm C, you will receive temsirolimus by vein over 30-60 minutes on Days 1, 8,
15, and 22 of each cycle. You will be given standard drugs to help decrease the risk of side
effects. You may ask the study staff for information about how the drugs are given and their
risks.

Study Visits:

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

About Days 8 and 22 of Cycle 1:

- You will have a physical exam.

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

If you are enrolled in Arm B and have Hodgkin lymphoma, on Days 8 and 28 of Cycle 1:

- You will have a needle tumor biopsy. This biopsy will be used for DNA testing and to
check for a response to the study drugs, as described above in the "Screening Tests"
section.

- Blood (about 1 tablespoon) will be drawn for biomarker testing.

About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

About Day 22 of Cycles 2 and beyond:

You will have a physical exam. Blood (about 2 teaspoons) will be drawn for routine tests.

Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for a
pregnancy test if you are able to become pregnant.

Every 8 weeks, you will have an x-ray, CT scan, MRI, 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 enrolled in Arm B and have Hodgkin lymphoma, at any point that the disease appears
to get worse:

- You will have a needle tumor biopsy. This biopsy will be used for DNA testing and to
check for a response to the study drugs, as described above in the "Screening Tests"
section.

- Blood (about 1 tablespoon) will be drawn for biomarker testing.

Length of Study:

You may continue taking the study drugs for as long as you are benefitting. You will be taken
off study if you experience intolerable side effects, the study doctor thinks it is in your
best interest, or the disease gets worse.

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 may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert
syndrome), ALT 2mg/dL

7. As the effect of sirolimus or everolimus or temsirolimus 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. The list of CYP3A4 inhibitors:
http://medicine.iupui.edu/clinpharm/ddis/clinical-table/

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