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

Primary Purpose

Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Anakinra

Denosumab

Everolimus

About this trial

This is an interventional treatment trial for Advanced Malignant Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).
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.
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.

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I (everolimus, anakinra)

Arm II (everolimus, denosumab)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Incidence of adverse events

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01624766

First Posted

June 19, 2012

Last Updated

February 24, 2021

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01624766

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

June 19, 2012 (Actual)

Primary Completion Date

February 24, 2021 (Actual)

Study Completion Date

February 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of anakinra or denosumab in combination with everolimus in patients with advanced cancers who progressed on standard therapy. SECONDARY OBJECTIVES: I. Preliminary assessment of antitumor efficacy of anakinra or denosumab in combination with everolimus in patients with advanced cancers. II. Assessment of the pharmacokinetic (PK) profile of anakinra or denosumab in combination with everolimus. III. Preliminary assessment of biomarkers. OUTLINE: This is a dose-escalation study of everolimus. Participants are assigned to 1 of 2 arms. ARM I: Participants receive everolimus orally (PO) daily and anakinra subcutaneously (SC) daily on days 1-28. Treatment repeats every 28 days in absence of disease progression or unacceptable toxicity. ARM II: 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. After completion of study treatment, participants are followed up at 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm, Refractory Malignant Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

57 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (everolimus, anakinra)

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm II (everolimus, denosumab)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Anakinra

Other Intervention Name(s)

Kinaret, Kineret, rIL-1ra, rIL1RN

Intervention Description

Given SC

Intervention Type

Biological

Intervention Name(s)

Denosumab

Other Intervention Name(s)

AMG 162, AMG-162, Prolia, Xgeva

Intervention Description

Given SC

Intervention Type

Drug

Intervention Name(s)

Everolimus

Other Intervention Name(s)

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

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) of everolimus

Description

Time Frame

At 28 days

Title

Incidence of adverse events

Description

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

Time Frame

Up to 30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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). 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Filip Janku

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center Website

Learn more about this trial

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

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