MSK 18-400 Glioblastoma

Full Name

A Phase II Trial of the PD-1 Antibody Nivolumab in Combination with Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma

Eligibility

Inclusion Criteria

Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing
MGMT hypermethylation in archival tumor biopsy, determined by any CLIA-approved, DNA-based assay
Prior maximal feasible surgical resection of biopsy
Prior treatment with radiation and temozolomide chemotherapy
Pathologic and/or Radiographic evidence of recurrent disease
Circumscribed enhancing tumor ≤ 5.0 cm in largest diameter (T1 post contrast)
1 prior course of radiation therapy
Age ≥ 18 years
Karnofsky performance status ≥ 70%

Adequate bone marrow function

Hemoglobin ≥ 10g/dL
Absolute neutrophil count ≥ 1,500/mm 3
Absolute lymphocyte count ≥ 200/mm 3
Platelet count ≥ 100,000/mm3

Adequate liver function

Bilirubin <1.5 times upper limit normal (ULN)
AST and ALT ≤ 3 times ULN
Alkaline phosphatase ≤ 2 times ULN

Adequate renal function

BUN and Creatinine <1.5 times ULN

Exclusion Criteria

Infratentorial location of the recurrence
IDH mutated glioblastoma
More than one prior tumor recurrence after standard first-line therapy
Prior radiation to the brain within ≤ 4 months
Circumscribed enhancing tumor >5.0 cm in largest diameter (T1 post contrast)
Pulmonary embolus or deep vein thrombosis within preceding 2 months
Grade 2 or greater congestive heart failure
Unstable angina, myocardial infarction within past 12 months
Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
Nonhealing wound, ulcer or bone fracture
Prior spontaneous CNS hemorrhage (as determined from clinical history, CT, or MRI)
Uncontrollable hypertension
Requiring escalating or chronic supraphysiologic doses of corticosteroids (> 4 mg dexamethasone daily) for control of disease at the time of registration
Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent.
Previous or current treatment with bevacizumab
Hypersensitivity to nivolumab or bevacizumab or any of its excipients
Diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Known history of active TB (Bacillus Tuberculosis)
Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Known history of, or any evidence of active, non-infectious pneumonitis.
Active infection requiring systemic therapy.
Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Unable to undergo MRI of the brain (i.e. pacemaker or any other contraindication for MRIs).