The purpose of this study is to evaluate the effectiveness of Prostate Specific Membrane Antigen (PSMA ADC), as well as its safety and side effects for patients with advanced brain tumors. This study will also study how your body metabolizes (breaks down) PSMA ADC.
PSMA expression has been demonstrated in the tumor neovasculature of Glioblastoma Multiforme (GBM) by immunohistochemical staining. Strong reactivity to the antibody component of PSMA ADC was observed in the endothelial cells of new tumor blood vessels in GBM. Since the endothelial cells are located on the luminal surface of blood vessels, PSMA ADC does not need to cross the blood brain barrier to reach its target. Following binding and internalization of PSMA ADC, the cytotoxic component of PSMA ADC will be released and destroy the neovasculature that supports tumor growth. Therefore, PSMA ADC may be an active treatment for GBM. Bevacizumab, an inhibitor of angiogenesis, has been shown to be effective in improving progression-free survival as a single agent. Thus PSMA ADC, which targets tumor angiogenesis by a mechanism different from that of bevacizumab, may be a novel therapeutic modality for GBM. A phase 2 study of PSMA ADC is proposed for patients with GBM that have progressed after standard treatment that includes radiation, temozolomide and bevacizumab. A phase 1 study of PSMA ADC in prostate cancer is ongoing and a phase 2 dose level of 2.5 mg/kg IV every 3 weeks has been defined. Treatment after bevacizumab failure for patients with GBM is a major unmet medical need. If activity were demonstrated in this trial, a definitive randomized study would be proposed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
2.5 mg/kg, IV, over 60 minutes every 3 weeks
Rhode Island Hospital
Providence, Rhode Island, United States
UT Southwestern
Dallas, Texas, United States
Response Rate (Progression) for Patients With Glioblastoma That Have Progressed After Prior Treatment That Has Included Radiation, Temozolomide and Bevacizumab.
The response assessment in neuro-oncology (RANO) will be used to define radiographic response. (PD): A \>25% increase in tumor area (product of two diameters) OR appearance of a new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time frame: 3 months until progression, potentially up to 1 year
Number of Patients Who Experienced Toxicities (Adverse Events) Who Received PSMA ADC for Recurrent Glioblastoma.
Please note that toxicities outlined may not all be related to the treatment regimen.
Time frame: at least every 3 weeks for a maximum of 30 post coming off drug, approximately 6 months
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