Anakinra or Denosumab and Everolimus in Advanced Cancer

• Maximum Tolerated Dose (MTD) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  If more than 33% of patients enrolled at any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of patients in cohort develop DLT, this cohort will be considered the MTD.
  
  

Study Groups:

Dose escalation:

If you are found to be eligible to take part in this study, your doctor will decide if you will receive everolimus with anakinra or everolimus with denosumab. Once it is decided which combination you will receive, you will be assigned to a dose level based on when you join the study.

Up to 3 dose levels of everolimus with anakinra will be tested. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. Up to 6 participants will be enrolled at each dose level. This will continue until the highest tolerable dose of everolimus with anakinra is found.

One (1) dose level of everolimus with denosumab will be tested at first. Participants will receive the highest dose level. This is a dose level that has already been given off-study in clinical practice, and researchers have experience with it. If intolerable side effects are seen, up to 4 more lower dose levels may be studied. Each new group of participants will receive a lower dose than the group before it. Up to 6 participants will be enrolled at each dose level. This will continue until the highest tolerable dose of everolimus with denosumab is found.

Dose expansion:

Once the highest tolerable dose of everolimus either with anakinra or denosumab is found, up to 14 more participants may be enrolled to further study the safety of each combination of drugs at that dose and the level of effectiveness of the study drugs in a certain tumor group.

Study Drug Administration:

Each study cycle is 28 days.

You will take everolimus by mouth at the same time every day with or without food, swallowed whole with a glass of water.

If you receive anakinra, you will receive it by injection under the skin either to the upper arm, upper thigh, or stomach at the same time every day. The study doctor or nurse will teach you how to give the injections yourself.

If you receive denosumab, you will receive it by injection under the skin either to the upper arm, upper thigh, or stomach on Day 1 of each cycle.

Study Visits:

On about Day 15-21 of Cycle 1:

• Your medical history will be recorded, including any cancer symptoms.
• You will have a physical exam, including measurement of your weight and vital signs.
• Your performance status will be recorded.
• Blood (about 1 tablespoon) will be drawn for routine tests.
• Urine may be collected for routine tests if the study doctor thinks it is needed.

Before starting Cycles 2 and beyond:

• Your medical history will be recorded, including any cancer signs and symptoms.
• You will have a physical exam, including measurement of your weight and vital signs.
• Your performance status will be recorded.
• Blood (about 1 tablespoon) will be collected for routine tests.
• Urine may be collected for routine tests.

Before every odd cycle starting Cycles 3, 5, and beyond:

-Blood (about 1/2 tablespoon) will be drawn to check your immune system.

Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT scan to check the status of the disease. Blood (about 1 tablespoon) will be drawn for tumor marker testing. After at least 6 months of taking the study drugs, you may have CT, MRI, and/or PET/CT scan and blood drawn every 12 weeks (every 3 cycles) if the study doctor thinks it is needed.

If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test before starting each study cycle.

If you are receiving the combination of everolimus and denosumab, blood (about 1 tablespoon) may be drawn more often to check your mineral levels if the study doctor thinks it is needed.

Length of Dosing:

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 drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-up Visit:

You will have a follow-up-visit within 30 days after your last dose of study drugs. You will be asked about any current health problems you may have and if you have had any side effects. If your study doctor thinks it is needed, you may have follow-up for a longer period of time.

This is an investigational study. Everolimus is FDA approved and commercially available to treat pancreatic cancer that has gotten worse, advanced renal cell carcinoma, and a type of brain tumor called subependymal giant cell astrocytoma. Anakinra is FDA approved and commercially available for treatment of rheumatoid arthritis. Denosumab is FDA approved and commercially available to prevent bone problems in patients with solid tumors that have spread to the bone. The combination of everolimus either with anakinra or denosumab to treat advanced cancer is investigational.

Up to 147 patients will take part in this study. All will be enrolled at MD Anderson.