Anakinra or Denosumab and Everolimus in Advanced Cancer
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01624766 |
Recruitment Status
:
Active, not recruiting
First Posted
: June 21, 2012
Last Update Posted
: March 7, 2018
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- No Results Posted
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You are being asked to take part in this study because you have advanced cancer that has either gotten worse or is resistant to standard therapy.
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.
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.
Condition or disease | Intervention/treatment | Phase |
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Advanced Cancers | Drug: Everolimus Drug: Anakinra Drug: Denosumab | Phase 1 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 57 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | June 19, 2012 |
Estimated Primary Completion Date : | June 2020 |
Estimated Study Completion Date : | June 2021 |
Arm | Intervention/treatment |
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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.
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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:
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
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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.
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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:
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
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- Maximum Tolerated Dose (MTD) of Anakinra or Denosumab in Combination with Everolimus in Participants with Advanced Cancers [ Time Frame: 8 weeks ]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.
- Tumor Response of Anakinra or Denosumab in Combination with Everolimus in Participants with Advanced Cancers [ Time Frame: 4 months ]Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA-125 for patients with ovarian cancer), or (4) a partial response according to Choi criteria, i.e., decrease in size by 10% or more, or a decrease in the tumor density, as measured by Hounsfield units (HU), by more than or equal to 15% 49.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- 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).
- ECOG performance status </= 2
- Patients must be >/= 18 years of age.
- 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 (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); 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
- Oral examination and appropriate preventive dentistry will be performed prior to the initiation of denosumab therapy.
- Negative tuberculosis quantiferon test for anakinra arm.
- Negative serology for histoplasma, blastomycosis, and coccidiomycosis for anakinra arm.
- 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.
- 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.
- Patients must be able to understand and be willing to sign a written informed consent document.
Exclusion Criteria:
- 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.
- Patients with an active infection.
- Pregnant or lactating women.
- History of hypersensitivity to anakinra.
- History of hypersensitivity to denosumab.
- History of hypersensitivity to everolimus.
- History of hypersensitivity to any component of the formulation.
- Patients unwilling or unable to sign informed consent document.
- Patients treated with TNF antagonists.
- Patients with a history of active systemic fungal infection.
- Patients with liver disease Child Pugh classification B and C.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01624766
United States, Texas | |
University of Texas MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 |
Principal Investigator: | Filip Janku, MD, PHD | M.D. Anderson Cancer Center |
Additional Information:
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT01624766 History of Changes |
Other Study ID Numbers: |
2011-1043 NCI-2012-01156 ( Registry Identifier: NCI CTRP ) |
First Posted: | June 21, 2012 Key Record Dates |
Last Update Posted: | March 7, 2018 |
Last Verified: | March 2018 |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers Advanced Malignancies Metastatic Cancers Everolimus Afinitor |
RAD001 Anakinra Kineret Denosumab AMG 162 |
Additional relevant MeSH terms:
Neoplasms Everolimus Sirolimus Denosumab Interleukin 1 Receptor Antagonist Protein Antineoplastic Agents Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Bone Density Conservation Agents Antirheumatic Agents |