Anakinra or Denosumab and Everolimus in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01624766
First received: June 19, 2012
Last updated: March 18, 2014
Last verified: March 2014

June 19, 2012
March 18, 2014
June 2012
June 2017   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01624766 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Anakinra or Denosumab and Everolimus in Advanced Cancer
A Phase I Trial of Anakinra (IL-1 Receptor Antagonist) or Denosumab (Anti-RANKL Monoclonal Antibody) in Combination With Everolimus (mTOR Inhibitor) in Patients With Advanced Malignancies

The goal of this clinical research study is to find the highest tolerable dose of the combination of Afinitor (everolimus) either with Kineret (anakinra) or Xgeva (denosumab) that can be given to patients with advanced cancer. The safety of these drugs will also be studied.

Everolimus is designed to stop cells from dividing.

Anakinra is designated to block a protein that is involved in tumor development, new blood vessels growing, and spread of cancer.

Denosumab is designed to block the activity of a protein, which may prevent bone complications in cancer that has spread to the bone.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced Cancers
  • Drug: Everolimus

    Starting Dose (Everolimus + Anakinra): Everolimus 5 mg by mouth daily for a 28 day cycle.

    Starting Dose (Everolimus + Denosumab): Everolimus 10 mg by mouth daily for a 28 day cycle.

    Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalating Group.

    Other Names:
    • Afinitor
    • RAD001
  • Drug: Anakinra

    Starting dose: 100 mg subcutaneously daily for a 28 day cycle.

    Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalating Group.

    Other Name: Kineret
  • Drug: Denosumab

    Starting dose: 120 mg subcutaneously day 1 of a 28 day cycle.

    Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalating Group.

    Other Name: AMG 162
  • Experimental: Everolimus + Anakinra Dose Escalating Group:
    Starting doses: Everolimus 5 mg by mouth daily for a 28 day cycle. Anakinra 100 mg subcutaneously daily for a 28 day cycle.
    Interventions:
    • Drug: Everolimus
    • Drug: Anakinra
  • Experimental: Everolimus + Denosumab Dose Escalating Group
    Starting doses: Everolimus 10 mg by mouth daily for a 28 day cycle. Denosumab 120 mg subcutaneously on Day 1 of a 28 day cycle.
    Interventions:
    • Drug: Everolimus
    • Drug: Denosumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
147
Not Provided
June 2017   (final data collection date for primary outcome measure)

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 >/= 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).
  3. ECOG performance status </= 2
  4. Patients must be >/= 18 years of age.
  5. Patients must have adequate organ and marrow function defined as: absolute neutrophil count (ANC) >/= 1,000/mL, platelets >/=75,000/mL; creatinine clearance >/= 35 ml/min; total bilirubin </= 2 X ULN; ALT (SGPT) and or AST (SGOT) </= 5 X ULN Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT (SGPT) </= 8 X ULN; Fasting lipid profile: cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL Corrected calcium >/= 8.4 mg/dL; phosphorus >/= 2.5 mg/dL for denosumab
  6. Oral examination and appropriate preventive dentistry will be performed prior to the initiation of denosumab therapy.
  7. Negative tuberculosis quantiferon test for anakinra arm.
  8. Negative serology for histoplasma, blastomycosis, and coccidiomycosis for anakinra arm.
  9. Negative serology for active hepatitis B and C for anakinra arm. Patients with positive serology for hepatitis B might eligible if they are willing to take lamivudine preventive therapy.
  10. 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.
  11. 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. Treatment of pre-existing invasive fungal infections must be completed prior to starting treatment.
  2. Patients with an active infection.
  3. Pregnant or lactating women.
  4. History of hypersensitivity to anakinra.
  5. History of hypersensitivity to denosumab.
  6. History of hypersensitivity to everolimus.
  7. History of hypersensitivity to any component of the formulation.
  8. Patients unwilling or unable to sign informed consent document.
  9. Patients treated with TNF antagonists.
  10. Patients with a history of active systemic fungal infection.
  11. Patients with liver disease Child Pugh classification B and C.
Both
18 Years and older
No
Contact: Filip Janku, MD, PHD 713-563-1930
United States
 
NCT01624766
2011-1043, NCI-2012-01156
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: Filip Janku, MD, PHD UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP