A Study of 177Lu-PSMA-617 in People With Gliomas

Not Applicable

Recruiting

• Conditions: Glioma; Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4); Glioblastoma, IDH-wildtype; Diffuse Midline Glioma, H3 K27-Altered; Diffuse Hemispheric Glioma, H3 G34-mutant; Diffuse Pediatric-type High-grade Glioma, H3-wildtype and IDH-wildtype
• Interventions: Drug: Temozolomide; Drug: 177Lu-PSMA-617; Diagnostic Test: 68Ga-PSMA-PET scan/ MRI; Behavioral: Quality of Life Questionnaires

• Registration Number: NCT07223034
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

The researchers are doing this study to find out whether the radiopharmaceutical therapy (RPT) 177Lu-PSMA-617 is a safe treatment for people with IDH wild type glioma.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-10
• Study Start: 2025-10-27
• Study First Submitted: 2025-10-28
• Study First Submitted QC: 2025-10-28
• Last Update Submitted: 2025-10-28
• Study First Posted: 2025-10-31
• Last Update Posted: 2025-10-31
• Primary Completion: 2027-10
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Confirmed histologic diagnosis of a WHO grade 2-4 glioma that is IDH1 R132H-wildtype, including the following:

  • Diffuse astrocytoma, IDH-wildtype (grade 2-4)
  • Glioblastoma, IDH-wildtype
  • Diffuse midline glioma, H3 K27-altered
  • Diffuse hemispheric glioma, H3 G34-mutant
  • Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype PSMA positive pathological stain (by immunohistochemistry) of baseline (pre-radiotherapy) resection or biopsy sample

• Completion of standard of care therapy including surgery (for resectable tumors) and adjuvant EBRT for glioma

• Patients must be on a dose of 4 mg or less of dexamethasone (or dexamethasone equivalent steroid) for 5 days prior to first planned dose of radiopharmaceutical

• Age ≥ 18

• ECOG ≤ 2

• Serum creatinine level < 1.5 x ULN or EGFR > 60 mL/min

• Liver laboratory values: ALT and AST ≤ 2.5 x ULN; Albumin > 2 g/ dL; Bilirubin < 3 X ULN

• Normal organ and marrow function as defined as the following

  • Total white blood count > 3.0 K/mcL
  • ANC ≥ 1.5 K/mcL
  • Platelets ≥ 100 K/mcL
  • Hemoglobin ≥ 9 g/dL

• Adequate contraception prior to registration (see section 9.0)

• Ability to understand, and willingness to sign the informed consent.

Exclusion Criteria

• Patient known to harbor any other non-canonical IDH mutations (i.e., non-R132H)
• Target lesion within 5 mm of either the brainstem, optic chiasm or optic nerves Receipt of bevacizumab as part of the initial treatment for glioma
• Life expectancy less than 12 weeks
• Nonhealing wound, ulcer or bone fracture
• History of severe brain injury
• Patient not eligible for sequential MRI evaluations
• Patients with prior RT to > 25% of the skeleton or prior exposure to prior Radium223, Strontium89 or Samarium153 containing compounds
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients with known or suspected history of grade II or higher chronic kidney disease (CKD)
• Unable to tolerate the PSMA PET/MR or PSMA PET/CT
• History of viral hepatitis or chronic liver disease with active symptoms
• History of pituitary or adrenal dysfunction
• Previously diagnosed active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis)
• Any condition that in the opinion of the investigator, would preclude participation in this study
• Receipt of any other investigational agents or participation in a concurrent treatment protocol
• Known allergies, hypersensitivities, or intolerance to 68Ga-PSMA-11/177Lu-PSMA-617 or its inactive compounding components
• Current or planned pregnancy
• Refusal to comply with detailed contraception requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
177Lu-PSMA-617	Temozolomide	Patients will begin the first and second cycles of adjuvant Temozolomide (TMZ) the night before the first and second infusions of 177Lu-PSMA-617, respectively. Post-treatment, MRI of the brain will be obtained every 2 months, as per standard of care. A 68Ga-PSMA-PET scan will be performed with the MRI of the brain 1 month after the second cycle of 177Lu-PSMA-617 and again at evidence of disease progression.
177Lu-PSMA-617	177Lu-PSMA-617	Patients will begin the first and second cycles of adjuvant Temozolomide (TMZ) the night before the first and second infusions of 177Lu-PSMA-617, respectively. Post-treatment, MRI of the brain will be obtained every 2 months, as per standard of care. A 68Ga-PSMA-PET scan will be performed with the MRI of the brain 1 month after the second cycle of 177Lu-PSMA-617 and again at evidence of disease progression.
177Lu-PSMA-617	68Ga-PSMA-PET scan/ MRI	Patients will begin the first and second cycles of adjuvant Temozolomide (TMZ) the night before the first and second infusions of 177Lu-PSMA-617, respectively. Post-treatment, MRI of the brain will be obtained every 2 months, as per standard of care. A 68Ga-PSMA-PET scan will be performed with the MRI of the brain 1 month after the second cycle of 177Lu-PSMA-617 and again at evidence of disease progression.
177Lu-PSMA-617	Quality of Life Questionnaires	Patients will begin the first and second cycles of adjuvant Temozolomide (TMZ) the night before the first and second infusions of 177Lu-PSMA-617, respectively. Post-treatment, MRI of the brain will be obtained every 2 months, as per standard of care. A 68Ga-PSMA-PET scan will be performed with the MRI of the brain 1 month after the second cycle of 177Lu-PSMA-617 and again at evidence of disease progression.

Primary Outcome Measures

Name	Time	Method
Descriptively report the toxicity	up to 8 weeks post first infusion	using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	2 years	PFS will be defined as the time from treatment initiation to progression of disease as noted radiographically per RANO 2.0 criteria or death, whichever occurred first, and will be analyzed using the Kaplan-Meier method

Trial Locations

Locations (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities); 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities); 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities); 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities); 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities); 🇺🇸 Uniondale, New York, United States