Clinical Trials /

Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma

NCT03430791

Description:

Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Bevacizumab-naïve, Recurrent Glioblastoma
  • Official Title: A Phase II Trial of Combination Tumor Treating Fields, Nivolumab Plus/Minus Ipilimumab for Bevacizumab-naïve, Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 2017-ODI-002
  • NCT ID: NCT03430791

Conditions

  • Recurrent Glioblastoma

Interventions

DrugSynonymsArms
Nivolumab 240 mg IVNivolumab MonotheraphyNivolumab Monotherapy
Nivolumab 3 mg/kgNivolumab+IpilimumabNivolumab+Ipilimumab
Ipilimumab 1 mg/kgNivolumab+IpilimumabNivolumab+Ipilimumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab MonotherapyExperimentalNivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months
  • Nivolumab 240 mg IV
Nivolumab+IpilimumabExperimentalNivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months
  • Nivolumab 240 mg IV
  • Nivolumab 3 mg/kg
  • Ipilimumab 1 mg/kg

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate according to modified iRANO criteria
Time Frame:Analyses will occur 4 months after accrual of 15 patients for each arm.
Safety Issue:
Description:Overall response rate is the proportion of patients whose best overall response per modified iRANO criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baptist Health South Florida

Trial Keywords

  • bevacizumab-naïve
  • recurrent glioblastoma

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