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Adjuvant 177Lu-PSMA-617 Radiopharmaceutical Therapy with Temozolomide for the Treatment of IDH Wild Type Gliomas Expressing PSMA following Standard Treatment
Trial Status: active
This phase I trial studies the side effects of 177Lu-PSMA-617 radiopharmaceutical therapy (RPT) when given together with temozolomide following radiation therapy (adjuvant) and to see how well it works in treating patients with gliomas that do not have a mutation (change) in the IDH1 or IDH 2 genes (IDH wild type) and that express prostate-specific membrane antigen (PSMA) after standard treatment. RPT drugs, such as 177Lu-PSMA-617, may carry radiation directly to tumor cells and not harm normal cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. Giving adjuvant 177Lu-PSMA-617 RPT with temozolomide may be safe, tolerable, and/or effective in treating patients with IDH wild type gliomas expressing PSMA following standard treatment.
Inclusion Criteria
Confirmed histologic diagnosis of a World Health Organization (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 external beam radiation therapy (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
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Serum creatinine level < 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (EGFR) > 60 mL/min
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
Albumin > 2 g/ dL
Bilirubin < 3 X ULN
Total white blood count > 3.0 K/mcL
Absolute neutrophil count (ANC) ≥ 1.5 K/mcL
Platelets ≥ 100 K/mcL
Hemoglobin ≥ 9 g/dL
Adequate contraception prior to registration
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 radiation therapy (RT) to > 25% of the skeleton or prior exposure to prior radium Ra 223 (Radium223), strontium Sr-89 (Strontium89) or samarium Sm-153 (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/magnetic resonance (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 gallium Ga 68 gozetotide (68Ga-PSMA-11)/177Lu-PSMA-617 or its inactive compounding components
Current or planned pregnancy
Refusal to comply with detailed contraception requirements
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07223034.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Brandon Imber
Phone: 631-212-6346
PRIMARY OBJECTIVE:
I. To assess safety during protocol interventions up to 8 weeks post first infusion of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617). (Phase 1a/1b)
SECONDARY OBJECTIVES:
I. To assess progression free survival (PFS).
II. To assess associations between standardized uptake value (SUV) on baseline PSMA positron emission tomography (PET) imaging and lesional uptake of 177Lu-PSMA-617.
III. To assess dynamics of PSMA positivity at each phase of treatment for high-grade glioma patients treated with 177LuPSMA-617.
IV. To assess correlations between lesional uptake on PSMA PET imaging and magnetic resonance imaging (MRI) characteristics including enhancement and perfusion.
V. To assess radiographic response following combination treatment.
VI. To assess rates of radiographic radionecrosis following combination treatment at 2, 6 and 12 months after completion of protocol therapy.
VII. To assess rates of symptomatic radionecrosis following combination treatment at 2, 6 and 12 months after completion of protocol therapy.
EXPLORATORY OBJECTIVES:
I. To assess overall survival (OS).
II. To calculate the lesional dosimetry of 177Lu-PSMA-617 for glioma.
III. To analyze quality of life (QOL) following adjuvant RPT.
IV. To determine time to next therapeutic intervention outside of planned adjuvant temozolomide (TMZ).
V. To correlate outcomes with PSMA immunohistochemistry, PET parameters, dosimetry and genetic signatures using MSK-IMPACT and circulating tumor DNA (ctDNA).
OUTLINE:
Patients receive temozolomide orally (PO) daily on days 1-5 of each cycle and 177Lu-PSMA-617 intravenously (IV) over 10-15 minutes on day 2 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Approximately four weeks after cycle 2, patients undergo gallium-68 (68Ga) PSMA PET/computed tomography (CT) or PET/MRI and MRI. Patients with evidence of residual PSMA avidity above background and who tolerate the study drug may receive up to 4 additional monthly cycles of temozolomide and 177Lu-PSMA-617 in the absence of disease progression or unacceptable toxicity. Patients also undergo 68Ga PSMA PET/CT or PET/MRI during screening, CT/single photon emission computed tomography (SPECT) on study, and blood sample collection and MRI throughout the study.
After completion of study treatment, patients are followed up every 2 months for 12 months.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
