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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-01842 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2011-1043 | Other Identifier | M D Anderson Cancer Center |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anakinra | Biological | Given SC |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Filip Janku | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| MD Anderson Cancer Center Website | View source |
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| Denosumab | Biological | Given SC |
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| Everolimus | Drug | Given PO |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D012008 | Recurrence |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |
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| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| D019947 | Receptors, Interleukin-6 |
| D000069448 | Denosumab |
| D000068338 | Everolimus |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D018123 | Receptors, Interleukin |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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