Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4), Diffuse Hemispheric Glioma, H3 G34-mutant, Diffuse Midline Glioma, H3 K27-Altered, Diffuse Pediatric-type High-grade Glioma, H3-wildtype and IDH-wildtype, Glioblastoma, IDH-wildtype, Glioma
Conditions
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.
Interventions
DRUGTemozolomide
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.
DRUG177Lu-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.
DIAGNOSTIC_TEST68Ga-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
BEHAVIORALQuality of Life Questionnaires
baseline assessments, QOL surveys will be conducted with XeQOL and FACT-Br at 6 months and 12 months post treatment
Sponsors
Memorial Sloan Kettering Cancer Center
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Descriptively report the toxicity | up to 8 weeks post first infusion | using the Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
CONTACTBrandon Imber, MD
CONTACTThomas Kaley, MD
PRINCIPAL_INVESTIGATORBrandon Imber, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed