Research And Grants

Phase I/II Study of Lutathera in Pediatric and Young Adult Patients with Recurrent and/or Progressive High-Grade Central Nervous System (CNS) Tumors and Meningiomas which Express Somatostatin Type 2A Receptors and Demonstrate Uptake on DOTATATE

Background:

There is a critical need to develop new effective, well-tolerated therapies for children, adolescents, and young adults with refractory high-grade brain/spine tumors. Lutathera is a targeted radiotherapy which binds to tumor cells that express somatostatin receptors, causing tumor cell death through localized release of radiation, with minimal side effects. There is emerging evidence that many pediatric and young adult high-grade brain/spine tumors express somatostatin receptors (especially medulloblastoma and other embryonal tumors), making them ideal targets for this therapy. We are conducting a clinical trial investigating the safety and effectiveness of Lutathera in this patient population. Within the context of this trial, we will also (1) evaluate how somatostatin receptor expression varies across different brain/spine tumors and determine clinical, imaging, pathology, and genetic characteristics which correlate with that expression, (2) identify imaging and molecular biomarkers predictive of response to Lutathera and/or disease recurrence, and (3) perform radiation dosimetry to establish optimal dosing of Lutathera in children and young adults, ensuring adequate tumor penetration while minimizing toxicity.

Trial rationale, objectives, and design:

Lutathera has the potential for successful expansion to neuro-oncology given evidence that many pediatric and young adult brain/spine tumors have high levels of somatostatin receptors, show corresponding uptake on somatostatin receptor-labeled imaging, and have preliminary data suggesting tumor stabilization or shrinkage with this targeted radiotherapy in initial small studies. Minimal side effects were observed and this has been safely administered to pediatric patients. We are conducting a clinical trial of Lutathera in children and young adults with high-grade brain/spine tumors (medulloblastoma and other embryonal tumors, high-grade gliomas including DIPG, and anaplastic ependymomas) which have recurred or progressed after prior treatment. As shown in the study figure below, a two-part screening process will ensure that patient’s tumors express somatostatin receptors and are likely to respond to Lutathera: first, somatostatin receptors on the tumor cell surface will be measured using a specific somatostatin-receptor stain performed on tumor tissue (from any prior biopsy/resection) and assessed under the microscope; second, patients will undergo a type of imaging (DOTATATE PET) that detects tissue which contains somatostatin receptors. Patients who pass the screening steps will enroll on one of the two following arms of the trial, which will be open simultaneously. In both arms, Lutathera will be given once every 8 weeks through an IV in the outpatient setting (approximately 4 hours):

1) Phase I arm for pediatric patients aged 4 to <18 years, with a primary objective of assessing safety and determining the maximally tolerated dose of Lutathera in children with high-grade brain/spine tumors. Three potential dose levels will be investigated, starting at the FDA-approved adult dose, scaled by patients’ body surface area. Preliminary efficacy (tumor response) will also be studied.

2) Phase II arm for young adult patients aged ≥18 years, with a primary objective of evaluating the effectiveness of Lutathera (with regard to change in tumor size on imaging) in high-grade brain/spine tumors, when Lutathera is administered at the FDA-approved for adults.