Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

Advanced Cancer Clinical Trial

Official title: A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

• NCT number: NCT01087554
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 2010
• Completion date: August 18, 2026