Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Bevacizumab-naïve, Recurrent Glioblastoma

Summary: Phase II trial in which participants with bevacizumab-naïve, recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.

Detailed description: Phase II trial in which participants with bevacizumab-naïve, recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
  The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months.
  Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed World Health Organization Grade IV glioblastoma with supratentorial distribution.
  -  Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by RANO criteria, or documented recurrent glioblastoma on biopsy.
  -  Prior therapies including radiation and temozolomide.
  -  Only 1-2 prior treatments for recurrences are allowed. Resection of recurrent glioblastoma is not considered a prior treatment.
  -  Must be at least 12 weeks from radiotherapy or progression outside of the high-dose radiation target volume or unequivocal evidence of progressive tumor on biopsy.
  -  All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.
  -  Karnofsky Performance Status (KPS) ≥ 60
  -  Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:
  -  absolute neutrophil count ≥ 1,000/mcL
  -  platelets ≥ 100,000/mcL
  -  hemoglobin > 8.0 mg/dL
  -  total bilirubin ≤ 2.0 x upper limit of normal
  -  AST (SGOT)/ALT (SGPT) ≤2.5 × upper limit of normal
  -  creatinine or creatinine clearance ≥60 mL/min/1.73 m2 for creatinine >ULN
  -  Corticosteroid dose must be stable or decreasing for at least 5 days prior to enrollment.
  -  Ability to understand and the willingness to provide written informed consent.
  Exclusion Criteria:
  -  Infratentorial disease.
  -  Prior use of bevacizumab, ipilimumab or other CTLA-4 inhibitor, or TTFields.
  -  Tumors with known IDH1 or IDH2 mutations.
  -  History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.
  -  Current or planned participation in a study of an investigational agent or using an investigational device.
  -  Uncontrolled intercurrent illness that would limit compliance with study requirements.
  -  Active or life-threatening infection requiring intravenous or >2 weeks of systemic therapy.
  -  Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy requires a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis unless the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site.
  -  breastfeeding must be discontinued by enrollment on study.
  -  Uncontrolled HIV or AIDS is not allowed. Patients with known history of HIV but with undetectable viral load on antiretroviral therapy are allowed.
  -  CHF, or MI or hemorrhagic/ischemic stroke in the last 3 months.
  -  Active illicit drug use or diagnosis of alcoholism
  -  Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
  -  Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of start of treatment.
  -  Any significant autoimmune disorders expected to impact multiple or internal organs, excluding mild eczema or autoimmune thyroiditis treated with thyroidectomy and requiring systemic immunosuppressive or immunomodulatory therapy.
  -  Any implanted programmable cranial device, including reprogrammable ventriculoperitoneal shunt (VPS) or cochlear implants, that precludes use of TTFields (Optune) therapy.

Relevance to patient case: not relevant