Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors

Medulloblastoma Clinical Trial

Official title: Phase I/II Study of Lutathera in Patients With Recurrent and/or Progressive High-Grade Central Nervous System Tumors and Meningiomas That Demonstrate Uptake on DOTATATE PET

Status Recruiting

Clinical Trial Summary

This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4-12 years (Phase I) or older than 12 yrs (Phase II) to test its safety and efficacy, respectively.

Funding Source - FDA OOPD (grant number FD-R-0532-01)

Clinical Trial Description

Somatostatin receptors regulate cell growth through downstream modulation of both proliferation and apoptosis signaling pathways, and thus represent a potential therapeutic target. Lutathera (Lutetium [Lu]177 Dotatate) is a radionuclide therapy which binds type-2A somatostatin receptors (SST2A) and has recently gained FDA approval for the treatment of adult gastroenteropancreatic neuroendocrine tumors expressing SST2A.

High SST2A expression has been consistently observed in medulloblastoma and other embryonal tumors (75-100% of cases) as well as in some HGGs and anaplastic ependymomas (13-80%), with corresponding uptake on radiolabeled somatostatin receptor nuclear imaging (e.g. DOTATATE PET).

Emerging data has demonstrated treatment response (disease stabilization or regression) to somatostatin receptor-targeted therapy in children and young adults with relapsed medulloblastoma, HGG, meningioma, and brain metastases of neuroendocrine tumors, suggesting sufficient CNS penetration to achieve therapeutic benefit.

The proposed Phase I-II study will investigate the safety and efficacy of Lutathera treatment in patients whose tumors demonstrate uptake on DOTATATE PET (functional evidence of SST2A expression). In both Phase cohorts, Lutathera will be administered as an intravenous infusion on day 1 of each 8-week cycle for up to 4 cycles.

Phase I: (4-12 years) To determine the safety, define the dose-limiting toxicities, and establish the maximally tolerated dose (MTD)/ recommended Phase II dose (RP2D) of Lutathera in this patient population. The first cycle (first 8 weeks) will be used as the dose-limiting toxicity (DLT) observation period. The starting dose will be dose level 1, 200 mCi*(body surface area [BSA]/1.73m2), which corresponds to the BSA-adjusted FDA approved adult dosing of Lutathera (200 mCi every 8 weeks). Once the MTD/RP2D is established, an efficacy expansion cohort of up to 10 patients will be opened to determine the preliminary efficacy of the MTD/RP2D of Lutathera in this cohort.

Phase II: (>12 years) Enroll patients at the recommended adult dose of 200 mCi every 8 weeks to determine the anti-tumor activity of Lutathera at this dosing in this population. Response will be assessed on imaging (brain and/or spine MRI and DOTATATE PET) following every cycle. ;

Related Conditions & MeSH terms

• Anaplastic Ependymoma
• Central Nervous System Neoplasms
• Diffuse Intrinsic Pontine Glioma
• Embryonal Tumor
• Ependymoma
• Glioma
• High Grade Glioma
• Medulloblastoma
• Meningioma
• Neoplasms
• Nervous System Neoplasms
• Recurrence
• Recurrent Diffuse Intrinsic Pontine Glioma
• Recurrent Malignant Glioma
• Recurrent Medulloblastoma
• Recurrent Primary Central Nervous System Neoplasm
• Refractory Diffuse Intrinsic Pontine Glioma
• Refractory Malignant Glioma
• Refractory Medulloblastoma
• Refractory Primary Central Nervous System Neoplasm

• NCT number: NCT05278208
• Study type: Interventional
• Source: Nationwide Children's Hospital
• Contact: Leonie Mikael
• Phone: 16147223284
• Email: leonie.mikael@nationwidechildrens.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 21, 2022
• Completion date: November 2027