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Advanced Malignant NeoplasmPhase 1NCT01624766

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

A Phase 1 study testing Anakinra, Denosumab and Everolimus in people with Advanced Malignant Neoplasm and Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anakinra, Denosumab and Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteUnited States
Study dates
19 Jun 2012to 24 Feb 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Anakinra, Denosumab, Everolimus
Medical subject headings
Neoplasm Metastasis, Recurrence, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraBiological

    Also called Kinaret, Kineret, rIL-1ra, rIL1RN

    Given SC

  • DenosumabBiological

    Also called AMG 162, AMG-162, Prolia, Xgeva

    Given SC

  • EverolimusDrug

    Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001

    Given PO

Study groups in NCT01624766
Study groupRoleWhat they receive
Arm I (everolimus, anakinra)ExperimentalParticipants 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.
Receives: Biological: Anakinra; Drug: Everolimus
Arm II (everolimus, denosumab)ExperimentalParticipants 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.
Receives: Biological: Denosumab; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At 28 days

  2. Incidence of adverse events

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

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2012 (estimated)
  2. Study start19 Jun 2012
  3. Primary completion24 Feb 2021
  4. Study completion24 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01624766
Sponsor's protocol ID
2011-1043
Other IDs
NCI-2018-01842, 2011-1043
Status last verified
Feb 2021
First submitted
19 Jun 2012
Last updated
25 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anakinra, Denosumab and Everolimus in people with Advanced Malignant Neoplasm and Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of everolimus (time frame: At 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01624766.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.

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