Overview

Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

Status:
Active, not recruiting
Trial end date:
2021-05-01
Target enrollment:
0
Participant gender:
All
Summary
The goal of this clinical research study is to find the highest tolerable dose of the combination vorinostat given in combination with either sirolimus, everolimus or temsirolimus that can be given to patients with advanced cancer. The safety of this drug combination will also be studied. The Study Drugs: Vorinostat is designed to prevent or slow down the growth of cancer cells by blocking proteins. Everolimus is designed to stop cells from dividing. This may stop or slow the growth or spread of cancer cells. Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill them. Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells. This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Everolimus is FDA-approved and commercially available for the treatment of pancreatic neuroendocrine tumor, subependymal giant cell astrocytoma, and renal cell carcinoma. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. The combination of these drugs is investigational. Up to 249 patients will take part in this study. All will be enrolled at MD Anderson.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Treatments:
Everolimus
Histone Deacetylase Inhibitors
Sirolimus
Vorinostat
Criteria
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