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

• Sponsor: Heinrich Elinzano, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01856933
• Collaborator: Progenics Pharmaceuticals, Inc. (Industry), Rhode Island Hospital (Other), University of Texas (Other)
• Enrollment: 6
• Locations: 2
• Arm: 1
• Duration (Months): 21.1
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
GBM; Glioblastoma Multiforme; Gliosarcoma	Drug: PSMA ADC	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Response Rate (Progression) for Patients With Glioblastoma That Have Progressed After Prior Treatment That Has Included Radiation, Temozolomide and Bevacizumab. [3 months until progression, potentially up to 1 year]

   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

1. Number of Patients Who Experienced Toxicities (Adverse Events) Who Received PSMA ADC for Recurrent Glioblastoma. [at least every 3 weeks for a maximum of 30 post coming off drug, approximately 6 months]

   Please note that toxicities outlined may not all be related to the treatment regimen.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Rhode Island Hospital	Providence	Rhode Island	United States	02903
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Heinrich Elinzano, MD, Prinicipal Investigator, Brown University
• ClinicalTrials.gov Identifier: NCT01856933
• Other Study ID Numbers: 263
• First Posted: May 20, 2013
• Last Update Posted: Nov 23, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Heinrich Elinzano, MD, Prinicipal Investigator, Brown University: GBM; Glioblastoma Multiforme; Gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Gliosarcoma

Study Results

Participant Flow

Arm/Group Title	PSMA ADC
Arm/Group Description	2.5 mg/kg, IV, over 60 minutes every 3 weeks PSMA ADC: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	PSMA ADC
Arm/Group Description	2.5 mg/kg, IV, over 60 minutes every 3 weeks PSMA ADC: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 66.7%
>=65 years	2 33.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60.3
Sex: Female, Male (Count of Participants)
Female	2 33.3%
Male	4 66.7%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Progression

Arm/Group Title	PSMA ADC
Arm/Group Description	2.5 mg/kg, IV, over 60 minutes every 3 weeks PSMA ADC: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
Measure Participants	6
Number [participants]	6 100%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PSMA ADC
Arm/Group Description	2.5 mg/kg, IV, over 60 minutes every 3 weeks PSMA ADC: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
Measure Participants	6
Count of Participants [Participants]	6 100%

Adverse Events

Arm/Group Title	PSMA ADC
Arm/Group Description	2.5 mg/kg, IV, over 60 minutes every 3 weeks PSMA ADC: 2.5 mg/kg, IV, over 60 minutes every 3 weeks
All Cause Mortality
	PSMA ADC
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PSMA ADC
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
Investigations
eye disorder/ vision changes	1/6 (16.7%)	1
H/A	1/6 (16.7%)	1
Hypermagnesemia	1/6 (16.7%)	1
Hypokalemia	1/6 (16.7%)	1
Intratumoral hemorrhage	1/6 (16.7%)	1
Nausea	1/6 (16.7%)	1
Thrombocytopenia	2/6 (33.3%)	2
seizure	1/6 (16.7%)	1
UTI	1/6 (16.7%)	1
WBC	1/6 (16.7%)	1
confusion	1/6 (16.7%)	1
muscle weakness/weakness general	2/6 (33.3%)	2
dyspnea	1/6 (16.7%)	1
Facial muscle weakness	1/6 (16.7%)	1
CD4 Lymph count	2/6 (33.3%)	2
Lymphopenia	1/6 (16.7%)	1
Anorexia	1/6 (16.7%)	1
syncope	2/6 (33.3%)	2
pain	1/6 (16.7%)	1
perforation-sigmoid	1/6 (16.7%)	1
cholesterol	1/6 (16.7%)	1
creatinine	1/6 (16.7%)	1
hyperglycemia	1/6 (16.7%)	1
hypoalbumin	1/6 (16.7%)	1
troponin	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	PSMA ADC
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Investigations
AKI	1/6 (16.7%)	1
Alopecia	1/6 (16.7%)	1
ALT	2/6 (33.3%)	2
AST	1/6 (16.7%)	1
anemia	1/6 (16.7%)	1
edema, lower leg	1/6 (16.7%)	1
eye disorder/ vision changes	1/6 (16.7%)	1
fatigue	2/6 (33.3%)	2
H/A	1/6 (16.7%)	1
Hypermagnesemia	1/6 (16.7%)	1
Hypokalemia	1/6 (16.7%)	1
Hyponatremia	2/6 (33.3%)	2
Infection/shingles/thrush	2/6 (33.3%)	2
Nausea	1/6 (16.7%)	1
Neutrophil count	1/6 (16.7%)	1
Thrombocytopenia	2/6 (33.3%)	2
vomiting	1/6 (16.7%)	1
rash- torso	1/6 (16.7%)	1
parathesia/neuropathy	1/6 (16.7%)	1
rash- papular	1/6 (16.7%)	1
urinary incontinence	1/6 (16.7%)	1
right ankle swelling	1/6 (16.7%)	1
UTI	1/6 (16.7%)	1
WBC	3/6 (50%)	3
intracerebral hematoma	1/6 (16.7%)	1
Lymphopenia	2/6 (33.3%)	2
dysphasia	2/6 (33.3%)	2
gait disturbance	1/6 (16.7%)	1
cognitive disturbance/impairment	2/6 (33.3%)	2
dysgeusia (taste)	1/6 (16.7%)	1
pain- left calf/leg	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.