BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)

This study has been completed.
Sponsor:
Collaborators:
Progenics Pharmaceuticals, Inc.
Rhode Island Hospital
University of Texas
Information provided by (Responsible Party):
Heinrich Elinzano, MD, Brown University
ClinicalTrials.gov Identifier:
NCT01856933
First received: January 8, 2013
Last updated: June 23, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
GBM
Glioblastoma Multiforme
Gliosarcoma
Drug: PSMA ADC
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Response Rate (Progression) for Patients With Glioblastoma That Have Progressed After Prior Treatment That Has Included Radiation, Temozolomide and Bevacizumab. [ Time Frame: 3 months until progression, potentially up to 1 year ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Toxicities (Adverse Events) of PSMA ADC for Patients With Recurrent Glioblastoma. [ Time Frame: at least every 3 weeks for a maximum of 30 post coming off drug, approximtely 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: May 2013
Study Completion Date: February 2015
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PSMA ADC
2.5 mg/kg, IV, over 60 minutes every 3 weeks
Drug: PSMA ADC
2.5 mg/kg, IV, over 60 minutes every 3 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01856933

Locations
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
UT Southwestern
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Heinrich Elinzano, MD
Progenics Pharmaceuticals, Inc.
Rhode Island Hospital
University of Texas
Investigators
Principal Investigator: Heinrich Elinzano, MD Brown University
  More Information

No publications provided

Responsible Party: Heinrich Elinzano, MD, Prinicipal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01856933     History of Changes
Other Study ID Numbers: 263
Study First Received: January 8, 2013
Results First Received: March 5, 2015
Last Updated: June 23, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Brown University:
GBM
Glioblastoma Multiforme
Gliosarcoma

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Gliosarcoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on August 26, 2015