- -
INCLUSION CRITERIA:
- Histopathologically proven diagnosis of Ependymoma, Medulloblastoma, Parenchymal
Pineal Region Tumors (Pineoblastoma, Pineocytoma, Pineal Tumor of Intermediate
Differentiation, Papillary Tumor of the Pineal Region), Choroid Plexus Tumors
(Carcinoma, Papilloma, Atypical Papilloma), Histone Mutated Gliomas, Gliomatosis
Cerebri, ATRT, Malignant/Atypical Meningioma*, Gliosarcoma or Primary CNS Sarcoma,
Pleomorphic Xanthoastrocytoma (PXA) and Anaplastic Pleomorphic Xanthoastrocytoma
(APXA), and tumors formerly known as Primitive Neuro-Ectodermal Tumors (Embryonal
Tumor with Multilayered Rosettes, Medulloepithelioma, CNS Neuroblastoma, CNS
Ganglioneuroblastoma, CNS Embryonal Tumor NOS; and tumor entities emerging from
methylation profiling of CNS-PNETs: CNS neuroblastoma with FOXR2 activation, CNS Ewing
sarcoma family tumor with CIC alteration, CNS high-grade neuroepithelial tumor with
MN1 alterations, and CNS high-grade neuroepithelial tumor with BCOR alteration) prior
to registration.
*Patients with extra CNS metastases from meningioma will be eligible even if pathology
review fails to demonstrate high grade features on available tumor samples.
- - The tumor tissue (e.g., block or 20 unstained slides) must be available to be sent for
immunophenotyping by NCI Laboratory of Pathology.
- - Participants must have progressive tumor growth after having received established
standard of care and/or other experimental treatments for their newly diagnosed or
recurrent disease.
Participants will be enrolled into 2 different cohorts (cohort 1 or
heavily pretreated; cohort 2 or not heavily pretreated).
- - Karnofsky performance status >= 70 within 14 days prior to Step 2 registration;
Participants with severe paraparesis/paraplegia who need minimal assistance for
selfcare due to their motor deficit but are otherwise functionally independent will be
considered eligible.
- - Adequate hematologic function based on CBC/differential within 14 days prior to Step 2
registration defined as follows:
- Absolute neutrophil count >= 1,500 cells/mm3;
- Platelet count >= 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 <= 30 mg/dl and.
- - Serum creatinine <= 1.7 mg/dl.
Note: If the serum creatinine is greater than 1.7 mg/dl, a 24-hour urine creatinine
clearance will be obtained and if the result of this study is within normal limits*, the
patient would be eligible to enroll onto study. (*Normal Creatinine Clearance Range: Male:
90
- - 130 ml/min; Female: 80 - 125 ml/min)
- 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) <= 2.0 mg/dl
and.
- - ALT and AST <= 2.5x ULN.
- - No active or chronic hepatitis infection.
HCV antibody (for Hepatitis C) and Hepatitis
B Surface antigen and Hepatitis B core antibody 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 participant must not be on a corticosteroid dose greater than physiologic
replacement dosing defined as 30 mg of cortisone per day or its equivalent.
- - The participant 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.
NOTE: Based on the evidence cited in Nivolumab IB ver. 20, given that nivolumab is not a
genotoxic agent, and that relevant systemic concentrations sufficient to produce a risk of
fetal toxicity are not expected in WOCBP partners from exposure to a male participant s
seminal fluid, male study participants will not be required to use contraceptive measures
and/or a latex or other synthetic condom during sexual activity with a WOCBP partner.
EXCLUSION CRITERIA:
- - Participants who are receiving any other investigational agents.
- - Prior use of an immunotherapy such as (but not limited to) a vaccine therapy,
dendritic cell vaccine, other checkpoint inhibitors, or intracavitary or convectional
enhanced delivery of chemotherapy.
- - Prior or concurrent malignancy unless its natural history or treatment does not have
the potential to interfere with the safety or efficacy assessment of the
investigational regimen.
- - 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 >= 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, with the exception of pericavitary
ischemia due to tumor resection.
- - 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 participants 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.
- - Participants 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 participants 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 participants 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, participants with vitiligo, endocrine deficiencies including thyroiditis managed
with replacement hormones including physiologic corticosteroids are eligible. Participants
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.
- - Participants unable to have MRIs.
