Targeted LSAM-Cisplatin Infusion in Gliomas, Evaluation of Response (TIGER-1)

Inclusion Criteria:

• Aged 3 to ≤ 21 years.
• Diagnosis of diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), based on characteristic magnetic resonance imaging (MRI) findings and/or histopathologic confirmation.
• Prior radiation treatment must have included focal radiation therapy per institutional standard of care and must have been initiated within 6 weeks of diagnosis.
• At least 4 weeks, but no more than 12 weeks, post-completion of radiotherapy treatment.
• A standard of care post-radiation magnetic resonance imaging (MRI) performed 4 to 6 weeks after radiation therapy is required for confirmation of eligibility.
• Performance status [Karnofsky Performance Scale or Lansky Performance Score] within 14 days of Day 1 ≥ 60.
• Absence of other significant medical condition.
• A legal parent/guardian and/or participant must be able to understand and be willing to sign a written informed consent and/or assent document, as appropriate.

Exclusion Criteria:

• Untreated symptomatic hydrocephalus at the time of consent, has metastatic or disseminated disease, or leptomeningeal disease.
• Magnetic resonance imaging (MRI) findings that preclude stereotactic procedure.
• Intercurrent illnesses or conditions which preclude participation: active systemic infections, autoimmune disease requiring systemic immunomodulation, active or uncontrolled seizure disorder, central nervous system (CNS) vasculopathy or aneurysms, Grade ≥3 cardiac dysfunction, Fridericia-corrected QT interval (QTcF) ≥470 ms.

• Abnormal organ function:

  • Renal insufficiency: glomerular filtration rate (GFR) ≤ 60 mL/min/1.73m² (with Schwartz equation)
  • Hepatic dysfunction: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of liver metastases; or bilirubin ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of Gilbert disease

  • Bone marrow suppression:

    • absolute neutrophil count (ANC) < 1,000/μL
    • platelets < 100,000/μL
  • Coagulopathy or international normalized ratio (INR) > 1.5
• Receiving any anticoagulants or antiplatelet drugs; any drugs known to cause ototoxicity and nephrotoxicity; receiving any other tumor-directed therapy.
• Known allergy or hypersensitivity to the study agent (including cisplatin and diluent components).
• Female participants of childbearing potential must not be pregnant or breast-feeding.