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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Enrolling; Phase 1

Conditions: Glioma; Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4); Diffuse Pediatric-type High-grade Glioma, H3-wildtype and IDH-wildtype; Diffuse Hemispheric Glioma, H3 G34-mutant; Glioblastoma, IDH-wildtype; Diffuse Midline Glioma, H3 K27-Altered

Treatments: Behavioral: Quality of Life Questionnaires; Drug: 177Lu-PSMA-617; Drug: Temozolomide; Diagnostic Test: 68Ga-PSMA-PET scan/ MRI

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07223034

25-169

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

177Lu-PSMA-617

Experimental group

Description:

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.

Treatment:

Diagnostic Test: 68Ga-PSMA-PET scan/ MRI

Drug: Temozolomide

Drug: 177Lu-PSMA-617

Behavioral: Quality of Life Questionnaires