Everolimus and Anakinra or Denosumab in Treating Participants With Relapsed or Refractory Advanced Cancers

NCT01624766 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2011-1043NCI-2018-01842
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of everolimus when given together with anakinra or denosumab in treating participants with cancers that have spread to other places in the body and have come back or aren't responding to treatment. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Anakinra is designated to block a protein that is involved in tumor development, new blood vessels growing, and the spread of cancer. Monoclonal antibodies, such as denosumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and anakinra or denosumab may work better in treating participants with advanced cancers.

Conditions

Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Malignant Neoplasm; Refractory Malignant Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of everolimus

  If more than 33% of patients enrolled at any particular dose level develop dose limiting toxicity (DLT), the treatment will continue at the dose level immediately below. If not more than 33% of the patients in the cohort develop DLT, this cohort will be considered the MTD. Only DLTs within course 1 (4 weeks) will be counted with respect to the dose-escalation algorithm.

  At 28 days

• Incidence of adverse events

  Describing the toxicity profile, descriptive statistics will be provided on the grade and type of toxicity by dose level.

  Up to 30 days

Study Arms (2)

Arm I (everolimus, anakinra)

EXPERIMENTAL

Participants receive everolimus PO daily and anakinra SC daily on days 1-28. Treatment repeats every 28 days in absence of disease progression or unacceptable toxicity.

Biological: Anakinra; Drug: Everolimus

Arm II (everolimus, denosumab)

EXPERIMENTAL

Participants receive everolimus PO daily on days 1-28 and denosumab SC on day 1. Treatment repeats every 28 days in absence of disease progression or unacceptable toxicity.

Biological: Denosumab; Drug: Everolimus

Interventions

Anakinra BIOLOGICAL

Given SC

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN

Arm I (everolimus, anakinra)

Denosumab BIOLOGICAL

Given SC

Also known as: AMG 162, AMG-162, Prolia, Xgeva

Arm II (everolimus, denosumab)

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Arm I (everolimus, anakinra); Arm II (everolimus, denosumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2.
• Absolute neutrophil count (ANC) \>= 1,000/mL.
• Platelets \>= 75,000/mL.
• Creatinine clearance \>= 35 ml/min.
• Total bilirubin =\< 2 X upper limit of normal (ULN) (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome). Exception for patients with liver metastasis: total bilirubin =\< 3 x ULN.
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) and or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 5 X ULN. Exception for patients with liver metastasis: ALT (SGPT) =\< 8 X ULN.
• Fasting lipid profile: cholesterol =\< 350 mg/dL.
• Fasting lipid profile: 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 Coccidioidomycosis for anakinra arm.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence; Neoplasms

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; Denosumab; Everolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Filip Janku

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: June 19, 2012
• Primary Completion: February 24, 2021
• Study Completion: February 24, 2021
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

US (1)