BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)
Condition: GBM; Glioblastoma Multiforme; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: PSMA ADC
Intervention description: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GBM; Glioblastoma Multiforme; Gliosarcoma

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females Histologically confirmed GBM (Patients with gliosarcoma are also
             eligible)

          -  Assessable or measurable disease by MRI

          -  Progression after prior treatment that includes radiation, temozolomide and
             bevacizumab.

             -> 4 weeks since prior chemotherapy, bevacizumab and other systemic treatment and > 3
             weeks from prior radiation.

          -  age >18 years

          -  Weight < 150 kg.

          -  Karnofsky performance score > 60

          -  Life expectancy >12 weeks

          -  Brain MRI within 21 days prior to registration

          -  Laboratory results requirements

               -  Absolute neutrophil count (ANC) ≥ 1000/mm3.

               -  Platelets (Plt) ≥ 100,000/mm3

               -  Hemoglobin (Hgb) ≥ 8.0 g/dL

               -  Total bilirubin ≤ 2.0 mg/dL

               -  Serum alanine transferase/ Serum aspartate transaminase (ALT/AST) ≤ 2.5x the
                  upper limit of normal (ULN)

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Pancreatic Amylase (p-amylase) ≤ the ULN

               -  Negative serum pregnancy test for women of child-bearing potential

          -  Stable corticosteroid dose at least 14 days prior to registration

          -  Women of childbearing potential must have a negative pregnancy test.

          -  Men and women of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

          -  Patients must not be on enzyme-inducing anti-epileptic drugs (EIAED). Patients may be
             on non-enzyme inducing anti-epileptic drugs (NEIAED) or may not be taking any
             anti-epileptic drugs. A list of AED that cause modest or no induction of hepatic
             metabolic enzymes will be discussed

        Exclusion Criteria:

          -  Non-GBM primary invasive malignant neoplasm within the five years prior to screening
             except for:

               -  keratinocyte (non-melanoma) (i.e., basal cell, squamous cell) carcinoma of the
                  skin; or low-grade papillary superficial transitional cell carcinoma of the
                  bladder.However, patients with stage 1 cancers not requiring cancer therapy
                  including chemotherapy or hormone therapy, for which a lifespan of greater than 3
                  years without treatment is expected (such as early stage prostate cancer) may be
                  enrolled.

          -  Clinically significant cardiac disease (New York Heart Association Class III/ IV or
             severe debilitating pulmonary disease

          -  Subjects with QTc>500 msec (either Bazzett's or Fridericia's method)

          -  Radiation therapy, cytotoxic chemotherapy, bevacizumab or other treatment for GBM
             within previous three weeks

          -  Evidence of an active infection requiring ongoing intravenous antibiotic therapy

          -  Any toxicity ≥ grade 2 (non-laboratory) (NCI CTCAE, Version 4.03) prior to first dose
             of study drug

          -  Prior treatment with PSMA ADC or other therapies targeting PSMA, or other anti-body
             drug conjugate (ADC) products that contain monomethyl auristatin E (MMAE) (e.g.,
             brentuximab vedotin, glembatumumab vedotin, ASG-5ME)

          -  Known hypersensitivity reactions to PSMA ADC or any of its components.

          -  Any medical condition that in the opinion of the Investigator may interfere with a
             subject's participation in or compliance with the study

          -  Patients with a prior history of pancreatitis