This study will enroll children and young adults (aged 2-25 years) with recurrent or progressive low-grade gliomas (LGG) who will undergo Laser Interstitial Thermal Therapy (LITT) with an FDA approved/cleared device. The primary objective is to estimate proportion of patients with recurrent or progressive LGGs who do not exhibit further disease progression at 15 months post-LITT compared to baseline MRI. Enrollment will require central imaging review to determine the eligibility of the lesion and amenability to LITT.

Pediatric low-grade gliomas (LGGs) are the most common brain tumors in children and adolescents, often presenting significant long-term treatment challenges. Surgical resection remains the cornerstone of treatment, but complete removal is not always feasible, resulting in suboptimal progression-free survival (PFS) and a high risk of treatment-related complications. Standard therapies, including chemotherapy regimens such as carboplatin and vincristine, have shown limited effectiveness, underscoring the need for improved treatment options. Recent advancements in molecularly targeted therapies, particularly Ras-MAPK pathway inhibitors like selumetinib, dabrafenib, and trametinib, have demonstrated promising outcomes. However, their long-term efficacy and safety are yet to be fully established, and the necessity for prolonged treatment, along with the potential for variable side effects, may significantly impact patients’ quality of life.

LITT offers a minimally invasive alternative with the potential to effectively treat LGGs by inducing localized tumor necrosis while preserving surrounding healthy tissue. LITT has shown tremendous promise in large studies of adult brain tumors and smaller studies in pediatric series, however its application in pediatric LGGs lacks rigorous study. This Phase 2 trial aims to assess disease progression rate of LITT in children, adolescents, and young adults with recurrent or progressive LGGs. These results will provide prospective data on treatment response of LITT for LGGs that will be used in future decisions to improve outcomes and quality of life for this challenging patient population.

To estimate the proportion of patients with recurrent or progressive LGGs who do not exhibit further disease progression at 15 months post-LITT.

Inclusion Criteria

• Participants must have recurrent or progressive pediatric LGG who have received at least one prior treatment. Prior treatment may include surgery alone and/or systemic therapy.
• Participants must have histologically confirmed LGG that is recurrent or progressive after prior treatment and determined to be a candidate for LITT by central review. All patients will undergo central review prior to LITT. Any number of previous recurrences are permissible provided the participant meets other enrollment criteria.
• Tumor size: up to 5 cm in largest dimension not including any cystic component.
  • Larger tumors will need to be discussed with the study team.
  • Additional adjunctive interventions such as cyst aspiration prior to or concurrent with a LITT procedure is allowed at the treating surgeon’s discretion.
• Tumor location: Tumors must be located in areas of the brain or central nervous system that are accessible and considered safe for LITT, as determined by central review.
  • Suprasellar gliomas not arising from the optic pathway are eligible.
  • Multifocal or metastatic LGGs are eligible, provided that the growing lesions are suitable for LITT.
  • Exophytic brainstem lesions, which are more accessible and present a lower risk, may be eligible for LITT.
  • A patient with stable leptomeningeal disease and a separate growing lesion suitable for LITT is eligible for the study.
• Prior Therapy: Participants may have had LITT for other medical indications, provided that the lesion being considered for this study has not previously undergone LITT, except for patients who have received LITT for an intracranial lesion that has shown progression post-LITT beyond 15 months would be eligible.
• Participants must have fully recovered from the acute toxic effects of all prior chemotherapy or targeted therapy prior to entering this study and would be eligible for surgical intervention per institutional guidelines.
  • Bevacizumab: participants must have received last dose > 21 days prior to study registration.
  • Participants must have had chemotherapy > 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration.
  • Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such patients should also be discussed with study chairs.

• Radiation:
  • Participants must have:

• • • Had their last fraction of local irradiation or focal radiosurgery to primary tumor ≥12 weeks prior to registration.
    • Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12 weeks prior to registration
• Age ≥ 2 years to ≤ 25 years of age
• Performance Score: Karnofsky ≥ 50 for participants > 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age (See Appendix A). Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
• Patients must be surgically eligible per institutional standards.
• Patients must co-enroll to PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.
• A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion Criteria

• Any contraindication to the use of LITT, such as but not limited to:
  • Optic pathway gliomas
  • Spinal tumors
  • Brainstem Lesions: Infiltrative brainstem lesions are excluded. However, exophytic brainstem lesions, which are more accessible and present a lower risk, may be eligible for LITT.
  • Any lesion/location determined by central review to be contraindicated for LITT.
• The presence of uncontrolled leptomeningeal disease or extracranial disease including:
  • Evidence of untreated obstructive hydrocephalus or mass effect causing >10mm midline shift
  • Presence of symptomatic intratumoral hemorrhage (Grade 3 & 4). Intratumoral hemorrhage grade 2 needs to be discussed with study team.
• Participants who are receiving any other investigational agents.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.

Funding is provided by UCSF Investigator Funds, PNOC Foundation, Monteris Medical, and Humor to Fight the Tumor Foundation.