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

Primary Purpose

GBM, Glioblastoma Multiforme, Gliosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PSMA ADC
Sponsored by
Heinrich Elinzano, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GBM focused on measuring GBM, Glioblastoma Multiforme, Gliosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rhode Island Hospital
  • UT Southwestern

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PSMA ADC

Arm Description

2.5 mg/kg, IV, over 60 minutes every 3 weeks

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
January 8, 2013
Last Updated
November 22, 2021
Sponsor
Heinrich Elinzano, MD
Collaborators
Progenics Pharmaceuticals, Inc., Rhode Island Hospital, University of Texas
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1. Study Identification

Unique Protocol Identification Number
NCT01856933
Brief Title
BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)
Official Title
BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Heinrich Elinzano, MD
Collaborators
Progenics Pharmaceuticals, Inc., Rhode Island Hospital, University of Texas

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GBM, Glioblastoma Multiforme, Gliosarcoma
Keywords
GBM, Glioblastoma Multiforme, Gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PSMA ADC
Arm Type
Experimental
Arm Description
2.5 mg/kg, IV, over 60 minutes every 3 weeks
Intervention Type
Drug
Intervention Name(s)
PSMA ADC
Intervention Description
2.5 mg/kg, IV, over 60 minutes every 3 weeks
Primary Outcome Measure Information:
Title
Response Rate (Progression) for Patients With Glioblastoma That Have Progressed After Prior Treatment That Has Included Radiation, Temozolomide and Bevacizumab.
Description
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
Secondary Outcome Measure Information:
Title
Number of Patients Who Experienced Toxicities (Adverse Events) Who Received PSMA ADC for Recurrent Glioblastoma.
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heinrich Elinzano, MD
Organizational Affiliation
Brown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
UT Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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