Laser thermal therapy for young people with low-grade glioma

PNOC042: A Phase 2, Multi-institutional Trial, Evaluating the Efficacy of Laser Interstitial Thermal Therapy (LITT) in Children, Adolescents and Young Adults With Recurrent or Progressive Low-grade Gliomas (LGG)

This research will test whether laser interstitial thermal therapy (LITT) can stop or slow recurrent or progressive low-grade gliomas in children, adolescents, and young adults.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 2 Years to 25 Years
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, Radiation
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT07506239 on ClinicalTrials.gov

What this trial studies

This interventional protocol treats children, adolescents, and young adults with recurrent or progressive low-grade gliomas using laser interstitial thermal therapy (LITT), a minimally invasive MRI-guided ablation technique. Eligible patients must have histologically confirmed recurrent LGG after at least one prior treatment, tumors generally ≤5 cm (excluding cystic portions), and lesions located in areas deemed safe for LITT by central review. Participants undergo the LITT procedure and scheduled MRI and clinical follow-up for 24 months to measure progression status at 15 months, objective response, duration of response, time to next treatment, and procedure-related toxicities. Exploratory analyses will examine seizure outcomes, effects on cystic tumors, the impact of ablation extent and volume, and the need for steroids or bevacizumab for symptomatic post-ablation edema.

Who should consider this trial

Good fit: Ideal candidates are children, adolescents, or young adults with histologically confirmed recurrent or progressive low-grade glioma who have had at least one prior treatment, have tumors generally ≤5 cm excluding cystic components, and whose tumor location is judged accessible and safe for LITT by central review.

Not a fit: Patients with tumors that are too large, located in areas unsafe for LITT, those with high-grade transformation, or those unable to travel to the treatment center are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, LITT could offer a minimally invasive option to control tumor growth and delay or avoid further systemic or surgical treatments for some young patients with recurrent low-grade glioma.

How similar studies have performed: LITT has shown promising local control and acceptable safety in adult series and limited pediatric reports, but prospective data specifically for recurrent pediatric low-grade glioma are still limited.

Eligibility criteria

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. 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 Pediatric Neuro-oncology Consortium (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 \>10 millimeter (mm) 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.

Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Sabine Mueller, MD, PhD — University of California, San Francisco
• Study coordinator: PNOC Operations Office

Conditions Low-grade Glioma; Recurrent Low Grade Glioma; Low Grade Glioma of Brain; Pediatric Cancer; Interstitial Laser Therapy