Inclusion Criteria:
- - Patients must have a histologically confirmed diagnosis of a non-brainstem
high-grade glioma (NB-HGG, WHO Grade III or IV astrocytoma, oligodendrogliomas,
oligoastrocytomas, ependymomas) that is recurrent, progressive or refractory
following radiotherapy with or without chemotherapy.
Patients must be candidates for
standard of care surgical resection or biopsy.
- - Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in two dimensions.
- - Patients must have recovered from the acute treatment related toxicities (defined as
≤ grade 2 if not defined in eligibility criteria) of all prior chemotherapy,
immunotherapy, radiotherapy or any other treatment modality prior to entering this
study.
- - Patients must have received their last dose of known myelosuppressive anticancer
therapy greater than 21 days prior to enrollment.
- - Patients must have received their last dose of the investigational or biologic agent
≥ 7 days prior to study enrollment.
- - For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which
adverse events are known to occur.
The duration must be discussed with and
approved by the study chair.
- - Monoclonal antibody treatment and/or agents with prolonged half-lives: At least
three half-lives must have elapsed prior to enrollment.
- - Patients must have had their last fraction of:
- Craniospinal irradiation ≥ 3 months prior to enrollment.
- - Other substantial bone marrow irradiation ≥6 weeks prior to enrollment.
- - Local palliative XRT ≥2 weeks.
- - ≥ 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment.
*Patients with any history of allogeneic transplant are not eligible.
- - Patient must be ≥ 4 but ≤ 26 years of age at the time of enrollment.
- - Karnofsky ≥ 60% for > 16 years of age; Lansky ≥ 60% for children ≤ 16 years of age.
• Participants who are unable to walk because of neurologic deficits, but who are up
in a wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.
- - Patients must have adequate organ and marrow function as defined below:
- Absolute neutrophil count >1000 cells/μL.
- - Platelets >75,000 cells/μL(unsupported, defined as no platelet transfusion
within 7 days)
- Hemoglobin ≥8g/dl (may receive transfusions)
- Total bilirubin ≤1.5 times institutional upper limit of normal (ULN)
- ALT(SGPT) <3 x institutional upper limit of normal.
- - Serum creatinine based on age/gender as noted in Table 1 Patients that do not
meet the criteria below but have a 24hour Creatinine Clearance or GFR
(radioisotope or iothalamate) ≥ 70 ml/min/1.73 m2 are eligible.
- - INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as
long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- - aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as
PT or PTT is within therapeutic range of intended use of anticoagulants.
- - Pulmonary function - Pulse oximetry > 93% on room air and no evidence of
dyspnea at rest.
- - Patient must be a candidate for surgical resection or biopsy at the time of
enrollment.
The goal of surgical resection is both cytoreduction and tumor
debulking, or biopsy for diagnosis confirmation as part of standard of care.
- - Patients with neurological deficits should have deficits that are stable for a
minimum of 1 week prior to enrollment.
A baseline detailed neurological exam should
clearly document the neurological status of the patient at the time of enrollment on
the study.
- - Patients must be on a stable or decreasing dose of corticosteroids for 7 days prior
to enrollment.
A maximum dexamethasone dose of 0.1 mg/kg/day is allowed (4 mg
maximum), but preferably have been discontinued (inhaled or topical use of steroids
is allowed).
- - The effects of nivolumab on the developing human fetus are unknown.
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, for the
duration of study participation, and for 5 months after completion of nivolumab
administration. 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. Men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 5 months after completion of nivolumab administration.
Female subjects of childbearing potential must not be pregnant or breast-feeding. Female
patients of childbearing potential must have a negative serum or urine pregnancy test
within 72 hours prior to receiving the first dose of study medication. If the urine test
is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- - Ability to understand and the willingness to sign a written informed consent document.
Parents/Legally authorized representatives may sign and give informed consent on behalf
of study participants.
Exclusion Criteria:
- - Patients with evidence of leptomeningeal, primary spinal cord, or multicentric
disease.
- - Patients who have not recovered to ≤ Grade 1 or baseline from adverse events due to
prior anti-cancer therapy.
- - Patients who are receiving any other investigational agents.
- - Female subjects of childbearing potential must not be pregnant or breast-feeding.
Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 72 hours prior to receiving the first dose of study
medication. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
- - History of allergic reactions attributed to compounds of similar chemical or
biologic composition to nivolumab.
- - Prior treatment with an anti-PD-1, anti PD-L1 and anti-PD-L2, or anti-CTLA-4
antibody, or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways.
- - Patients who have had prior allogenic hematopoietic stem cell transplant.
- - Participants with an active, known, or suspected autoimmune disease.
Participants
with type I diabetes mellitus, hypothyroidism only requiring hormone replacement,
skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger
are permitted to enroll.
- - Patients with uncontrolled intercurrent illness or any other significant
condition(s) (serious infections or significant psychiatric, cardiac, pulmonary,
hepatic, or other organ dysfunction that in the opinion of the investigator would
compromise the patient's ability to tolerate protocol therapy, put them at
additional risk for toxicity, or would interfere with the study procedures or
results.
- - Patients who have had live vaccines within 30 days prior to the first dose of trial
treatment.
