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.
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.
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.
Renal insufficiency: glomerular filtration rate (GFR) ≤ 60 mL/min/1.73m² (with Schwartz equation)
Single group
LSAM-Cisplatin
DrugParticipants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), will receive a single intratumoral infusion of LSAM-Cisplatin 6 mg/mL via MRI-guided delivery at an infusion rate of 5 µL/min. Phase 1 (Dose Escalation): Participants will be enrolled sequentially into one of six dose levels. Volumes being delivered will range from 27 to 296 µL over a time period of 5 to 59 minutes. Phase 2 (Dose Expansion): Participants will receive LSAM-Cisplatin 6 mg/mL at the recommended Phase 2 dose (RP2D) selected based on the safety and tolerability findings from the dose-escalation phase.
Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability)
Treatment Emergent Adverse Events will be assessed by changes in adverse events, changes in concomitant medications, changes in laboratory values, and physical exams.
Objective Response Rate (ORR)
The proportion of participants with overall confirmed response of complete response (CR) or partial response (PR) as determined using Response Assessment in Pediatric Neuro-Oncology (RAPNO)/Response Assessment in Pediatric Neuro-Oncology for Diffuse Intrinsic Pontine Glioma (RAPNO-DIPG) criteria.
Progression-Free Survival (PFS)
Progression-Free survival (PFS) as assessed using Response Assessment in Pediatric Neuro-Oncology (RAPNO)/Response Assessment in Pediatric Neuro-Oncology for Diffuse Intrinsic Pontine Glioma (RAPNO-DIPG) criteria.
Overall Survival (OS)
Overall survival (OS) as determined by survival time post-infusion of LSAM-Cisplatin.
Concentration of Cisplatin in the Systemic Circulation Post-infusion
Cisplatin concentrations in plasma samples collected pre-infusion of LSAM-Cisplatin, and at 1, 2, 24, and 48 hours after completion of the LSAM-Cisplatin infusion, and at Weeks 1, 2, 3, 4, and 8.
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NanOlogy, LLC
Lead sponsor
WEP Clinical
Collaborator
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