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Nivolumab in People With IDH-Mutant Gliomas With and Without Hypermutator Phenotype

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ClinicalTrials.gov Identifier: NCT03718767
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Gliomas are the most common malignant brain tumors. Some have certain changes (mutations) in the genes IDH1 or IDH2. If there are a high number of mutations in a tumor, it is called hypermutator phenotype (HMP). The drug nivolumab helps the immune system fight cancer. Researchers think it can be more effective in patients with IDH1 or IDH2 mutated gliomas with HMP. They will test gliomas with and without HMP.

Objectives:

To see if nivolumab stops tumor growth and prolongs the time that the tumor is controlled.

Eligibility:

Adults 18 years or older with IDH1 or IDH2 mutated gliomas

Design:

Participants will be screened with:

Medical history

Physical exam

Heart, blood, and pregnancy tests

Review of symptoms and activity levels

Brain magnetic resonance imaging (MRI). Participants will lie in a cylinder that takes pictures in a strong magnetic field.

Tumor samples

Participants will get the study drug in 4-week cycles. They will get it through a small plastic tube in a vein (IV) on days 1 and 15 of cycles 1-4. For cycles 5-16, they will get it just on day 1.

On days 1 and 15 of each cycle, participants will repeat some or all screening tests.

After cycle 16, participants will have 3 follow-up visits over 100 days. They will answer health questions, have physical and neurological exams, and have blood tests. They may have a brain MRI.

Participants whose disease did not get worse but who finished the study drug within 1 year of treatment may have imaging studies every 8 weeks for up to 1 year.

Participants will be called or emailed every 6 months with questions about their health.


Condition or disease Intervention/treatment Phase
Glioma Glioblastoma High Grage Glioma Low Grade Glioma Malignant Glioma Drug: Nivolumab Phase 2

  Show Detailed Description

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Study Type : Interventional
Estimated Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Nivolumab for IDH-mutated Gliomas With Hypermutator Phenotype
Actual Study Start Date : March 27, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : August 27, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: 1/Nivolumab
Nivolumab is given IV as flat dose of 240 mg for Cycles 1-4 and 480 mg for Cycles 5-16.
Drug: Nivolumab
Nivolumab is given IV as flat dose of 240 mg for Cycles 1-4 and 480 mg for Cycles 5-16.




Primary Outcome Measures :
  1. 6-month progression free survival rate [ Time Frame: 6 months ]
    Proportion of patients that do not have progressive disease after 6 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients must have recurrent glioma (histologically confirmed by NIH Laboratory of Pathology) with IDH1 or IDH2 mutation (confirmed by DNA sequencing, FoundationOne is preferable for confirmation of mutation, but not necessary).
  • Patients must have tumor specific mutational load (number of somatic mutations per exome) performed at NIH. Must have either result of previous NIH testing or must provide adequate tissue sample for testing.
  • The tumor tissue (e.g. block or 15 unstained slides) must be available for molecular and immune profiling. Fresh or frozen tumor sample will be used if available, but not mandatory.
  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • Patient must be able to tolerate an MRI study with intravenous gadolinium contrast.
  • Karnofsky greater than or equal to 60%
  • Patients must have adequate organ and marrow function as defined below:

    • Absolute neutrophil count greater than or equal to 1,500/mcL
    • Platelet Count greater than or equal to 100,000/MCL
    • Hemoglobin greater than 9.0 g/dL (may be transfused to achieve this level)
    • BUN less than or equal to 30 mg/dL and
    • Serum creatinine less than or equal to 1.7 mg/dL
    • Total bilirubin (except patients with Gilbert s Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) less than or equal to 2.0 mg/dL
    • ALT and AST less than or equal to 2.5x institutional upper limit of normal.
  • The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 5 months (women) and 7 months (men) after the last dose of the drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • The patient must be able to understand and be willing to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • Patients who have a history of receiving immune therapy, such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years prior to initiation of study therapy.
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or CIDP, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn s, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.

    --Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sj(SqrRoot)(Delta)gren s syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.

  • The patient must not be currently on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (within timeframes identified in the bullets below) that would limit compliance with study requirements.
  • Known HIV-positive or acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS is based on the lack of information regarding the safety of nivolumab in patients with active HIV infection
  • Pregnant women are excluded from this study because nivolumab s potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab.
  • Known active, chronic or history of hepatitis infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03718767


Contacts
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Contact: Christine M Bryla, R.N. (240) 760-6007 brylacm@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jing Wu, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03718767     History of Changes
Other Study ID Numbers: 190006
19-C-0006
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 23, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
PD 1 Pathway
High Tumor Mutational Load
Immune Checkpoint
Quality of Life
Additional relevant MeSH terms:
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Glioma
Glioblastoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents