Fourth Ventricular Administration of Immune Checkpoint Inhibitor (Nivolumab) and Methotrexate or 5-Azacytidine for Recurrent Medulloblastoma, Ependymoma, and Other CNS Malignancies

Sponsor
Jeffrey Treiber
Study ID
NCT06466798
Phase
PHASE1
Status
Withdrawn

Conditions

  • CNS Malignancies
  • Recurrent Ependymoma
  • Recurrent Medulloblastoma

Eligibility Criteria

Sex
ALL
Age
1 Year - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    Nivolumab infusions will be given intraventricularly once every other week for 12 weeks. Dosing will be based upon patient body weight.
  • Methotrexate — DRUG
    2 mg methotrexate infusions will be given intraventricularly daily for 4 consecutive days per week every other week for 12 weeks.
  • 5-Azacytidine — DRUG
    10 mg 5-Azacytidine infusions will be given intraventricularly once weekly for twelve consecutive weeks.

Study Details

The goal of this clinical trial is to assess the safety, toxicity, and antitumor activity of fourth ventricular infusions of nivolumab plus 5-azacytidine for recurrent ependymoma and nivolumab plus methotrexate for recurrent medulloblastoma and other CNS malignancies. Additionally, the study will explore immunologic responses to nivolumab. The hypothesis is that local administration of nivolumab, an immune checkpoint inhibitor, is safe and will lead to even more robust treatment responses when administered following 5-azacytidine in patients with recurrent ependymoma or methotrexate in patients with medulloblastoma or other CNS tumors.

Key Dates

Start date
Jul 15, 2024
Status verified
Jan 2026
Primary completion
Jul 1, 2027
Completion
Jul 1, 2027

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Nivolumab plus Methotrexate
    Enrolled patients with medulloblastoma and other CNS malignancies will receive: 1. Intraventricular Methotrexate infusions 2 mg daily for 4 consecutive days per week every other week on weeks 1, 3, 5, 7, 9, and 11. 2. Intraventricular Nivolumab infusions. Nivolumab will be administered once every other week on weeks 2, 4, 6, 8, 10, and 12. Dosing will be based upon patient body weight.
  • Experimental: Nivolumab plus 5-Azacytidine
    Enrolled patients with ependymoma will receive: 1. Intraventricular 5-Azacytidine infusions 10 mg once weekly for twelve consecutive weeks. 2. Intraventricular Nivolumab infusions once every other week on weeks 1, 3, 5, 7, 9, and 11. Dosing will be based upon patient body weight.

Primary Outcome Measure

Safety as assessed by the number of participants with a new neurological toxicity that is graded as Grade 3 or higher and that is probably or definitely related to infusions [that is, classified as dose-limiting toxicity (DLT)] [ Time Frame: from start of treatment to end of treatment (about 12 weeks) ]

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