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Anakinra or Denosumab and Everolimus in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 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: June 27, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Drug: Everolimus
Drug: Anakinra
Drug: Denosumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Anakinra or Denosumab in Combination with Everolimus in Participants with Advanced Cancers [ 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.


Secondary Outcome Measures:
  • Tumor Response of Anakinra or Denosumab in Combination with Everolimus in Participants with Advanced Cancers [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 147
Study Start Date: June 2012
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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: 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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  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (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 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624766

Contacts
Contact: Filip Janku, MD, PHD 713-563-1930

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Filip Janku, MD, PHD M.D. Anderson Cancer Center
  More Information

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 
Study First Received: June 19, 2012
Last Updated: June 27, 2016
Health Authority: United States: Food and Drug Administration

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
Bone Density Conservation Agents
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 26, 2016