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Immune Checkpoint Inhibitor Nivolumab in People With Select Rare CNS Cancers

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ClinicalTrials.gov Identifier: NCT03173950
Recruitment Status : Recruiting
First Posted : June 2, 2017
Last Update Posted : July 4, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors.

Objectives:

To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.

Eligibility:

Adults whose rare CNS tumor has returned.

Design:

Participants will be screened:

  • Heart and blood tests
  • Physical and neurological exam
  • Hepatitis tests
  • Pregnancy test
  • MRI. They will lay in a machine that takes pictures.
  • Tumor tissue sample. This can be from a previous procedure.

At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.

Participants will get nivolumab in a vein every 2 weeks for up to 64 weeks.

Participants will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.

Genetic tests will be done on participants tumor tissue. Participants will be contacted if any clinically important results are found.

After treatment ends, participants will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....


Condition or disease Intervention/treatment Phase
Ependymoma Meningioma Chordoma Drug: Nivolumab Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of the Immune Checkpoint Inhibitor Nivolumab in Patients With Select Rare CNS Cancers
Actual Study Start Date : July 13, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: 1/Experimental Therapy
Participants will receive nivolumab at standard dose of240mg IV every 2 weeks for cycles 1 through 4, thendoses of 480mg every 4 weeks for a total of 12 additional doses
Drug: Nivolumab

Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks.

A maximum of 32 treatments will be given (64 weeks). A cycle will be defined as 2 treatments (4 weeks) and patients will undergo efficacy assessments using MR imaging every 2 cycles.





Primary Outcome Measures :
  1. objective response [ Time Frame: end of treatment ]
    Rate of achieving a confirmed Complete Response/Partial Response (confirmed by imaging one month later)

  2. progression free survival rate [ Time Frame: 6 months after end of treatment ]
    Rate of durable Stable Disease lasting at least 6 months (PFS-6)



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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:
  • Histopathologically proven diagnosis of Ependymoma, Medulloblastoma, Pineoblastoma/Pineocytoma, Choroid Plexus Carcinoma/Papilloma, Chordoma, Gliomatosis, Brainstem Glioma, Midline Glioma, ATRT, Atypical/Malignant Meningioma, Gliosarcoma or Primary Brain Sarcoma prior to registration as confirmed by NCI Laboratory of Pathology
  • The tumor tissue (e.g. block or 15 unstained slides) must be available to be sent for immunophenotyping.
  • Patients must have progressive tumor growth after having received established standard of care treatment for their disease
  • Age greater than or equal to 18;
  • Karnofsky performance status greater than or equal to 70 within 14 days prior to Step 2 registration;
  • Adequate hematologic function based on CBC/differential within 14 days prior to Step 2 registration defined as follows:

    • Absolute neutrophil count greater than or equal to 1,500 cells/mm3;
    • Platelet count greater than or equal to 100,000 cells/mm3
    • Hemoglobin > 9.0 g/dl (may be transfused to achieve this level)
  • Adequate renal function within 14 days prior to Step 2 registration defined as follows:

    • BUN less than or equal to 30 mg/dl and
    • Serum creatinine less than or equal to 1.7 mg/dl
  • Adequate hepatic function within 14 days prior to Step 2 registration defined as follows:

    • 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 and
    • ALT and AST less than or equal to 2.5x ULN
    • No active or chronic hepatitis infection. HCV antibody (for Hepatitis C) and Hepatitis B Surface antigen must be negative. This has been routinely incorporated into immunotherapy trials with checkpoint inhibitors because of concerns that the risk of treatment-induced hepatic injury is increased in the setting of active viral hepatitis.
  • The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.
  • The patient must provide study-specific informed consent prior to study entry. No Durable Power of Attorney or Next of Kin can provide initial consent.
  • The effects of nivolumab on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
  • Severe, active co-morbidity defined as follows:

    • Unstable angina within the last 6 months prior to Step 2 registration
    • Transmural myocardial infarction within the last 6 months prior to Step 2 registration
    • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of greater than or equal to 2 mm using the analysis of an EKG performed within 14 days prior to Step 2 registration
    • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to Step 2 registration
    • History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to Step 2 registration
    • Serious and inadequately controlled cardiac arrhythmia
    • Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Step 2 registration, with the exception of the craniotomy for tumor resection.
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    • Known 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.
    • Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity.
  • 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, should be excluded. 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 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. However, patients with vitiligo, diabetes mellitus, and Hashimoto thyroiditis on appropriate replacement therapy may be enrolled.

  • Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
  • Allergies and Adverse Drug Reaction: History of allergy to study drug components
  • Pregnancy or lactating females due to possible adverse effects on the developing fetus or infant due to study drug. Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to Step 2 registration.
  • History of severe hypersensitivity reaction to any monoclonal antibody.

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): NCT03173950


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

Locations
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
Principal Investigator: Mark R Gilbert, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03173950     History of Changes
Other Study ID Numbers: 170102
17-C-0102
First Posted: June 2, 2017    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: April 27, 2018

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) ):
Immunotherapy
Anti-PD-1 Antibody
Brain Tumors
MDASI-BT
Spinal Cord Tumors

Additional relevant MeSH terms:
Ependymoma
Meningioma
Chordoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs