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BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study

Phase 2
18 Years
Not Enrolling
GBM, Glioblastoma Multiforme, Gliosarcoma

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Trial Information

BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study

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.

Inclusion Criteria:

- Males and females Histologically confirmed GBM (Patients with gliosarcoma are also

- Assessable or measurable disease by MRI

- Progression after prior treatment that includes radiation, temozolomide and

-> 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate for patients with glioblastoma that have progressed after prior treatment that has included radiation, temozolomide and bevacizumab.

Outcome Time Frame:

3 months until progression, potentially up to 1 year

Safety Issue:


Principal Investigator

Rees Cosgrove, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brown University


United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

October 2014

Related Keywords:

  • GBM
  • Glioblastoma Multiforme
  • Gliosarcoma
  • GBM
  • Glioblastoma Multiforme
  • Gliosarcoma
  • Glioblastoma
  • Gliosarcoma



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