Targeted LSAM-Cisplatin Infusion in Gliomas, Evaluation of Response

Phase 1/2a Study to Determine the Safety of Intratumoral Infusion of Large Surface Area Microparticle (LSAM)-Cisplatin in Participants With Diffuse Midline Glioma (DMG), Including Diffuse Intrinsic Pontine Glioma (DIPG)

Open-label, dose-escalating, Phase 1/2a trial of Large Surface Area Microparticle (LSAM)-Cisplatin to treat participants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), via stereotactic infusion under intraoperative magnetic resonance imaging (MRI) guidance.

Large Surface Area Microparticle (LSAM)-Cisplatin consists of large surface area microparticles of the chemotherapy drug cisplatin. These microparticles are administered as a single-magnetic resonance imaging (MRI) guided infusion directly into the tumor to target cancer at the site of the disease with less systemic exposure than intravenously administered chemotherapy. In this study, all participants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), will receive LSAM-Cisplatin and will be evaluated to determine whether it is safe and has an effect on the tumor.

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.