Recruiting
Phase 1

177Lu-PSMA-617

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT07223034

Conditions

Glioma

Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4)

Glioblastoma, IDH-wildtype

Diffuse Midline Glioma, H3 K27-Altered

Diffuse Hemispheric Glioma, H3 G34-mutant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Temozolomide

177Lu-PSMA-617

68Ga-PSMA-PET scan/ MRI

Quality of Life Questionnaires

Study Details

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.

Conditions

Glioma

Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4)

Glioblastoma, IDH-wildtype

Diffuse Midline Glioma, H3 K27-Altered

Diffuse Hemispheric Glioma, H3 G34-mutant

Study ID

NCT07223034

Start date

Oct 27, 2025

Status verified date

Jun, 2026

Completion date

Oct, 2027

Anticipated

Primary completion date

Oct, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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
  • 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

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

Interventions

Temozolomide

Patients will begin taking Temozolomide orally on the first 5 days of each 28-day cycle. The first dose will be given the evening before the first infusion of 177Lu-PSMA- 617.

177Lu-PSMA-617

This agent will be given for 2-6 total doses, spaced 4 weeks (+/-1 week) apart. This will be administered on the 2nd day of the first two cycles of SOC adjuvant temozolomide.

68Ga-PSMA-PET scan/ MRI

Approximately 4 weeks after cycle 2 of radiopharmaceutical therapy (RPT), patients will undergo post-treatment imaging with 68Ga- PSMA PET and MRI

Quality of Life Questionnaires

baseline assessments, QOL surveys will be conducted with XeQOL and FACT-Br at 6 months and 12 months post treatment

Primary outcome measure

  • Descriptively report the toxicity [ Time Frame: up to 8 weeks post first infusion ]

Central Contacts and Locations

Central contacts

Brandon Imber, MD

631-212-6346imberb@mskcc.org

Thomas Kaley, MD

212-639-5122

Locations

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Recruiting

Harrison, New York, United States, 10604

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Recruiting

New York, New York, United States, 10065

Contacts

Brandon Imber, MD

631-212-6346

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Recruiting

Uniondale, New York, United States, 11553

Contacts

Brandon Imber, MD

631-212-6346

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Jun 4, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-06-04.