GBMPhase 2NCT01856933
BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)
A Phase 2 study testing PSMA ADC in people with GBM and Glioblastoma Multiforme, run by Heinrich Elinzano, MD at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GBM, Glioblastoma Multiforme, Gliosarcoma
- What is being tested?
- PSMA ADC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2013to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UT Southwestern
Dallas, Texas, 75235
Rhode Island Hospital
Providence, Rhode Island, 02903
About this study
Official title: BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study
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.
Read the 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.
- Conditions
- GBM, Glioblastoma Multiforme, Gliosarcoma
- Being tested
- PSMA ADC
- Keywords
- GBM, Glioblastoma Multiforme, Gliosarcoma
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PSMA ADCDrug
2.5 mg/kg, IV, over 60 minutes every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| PSMA ADC | Experimental | 2.5 mg/kg, IV, over 60 minutes every 3 weeks Receives: Drug: PSMA ADC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 months until progression, potentially up to 1 year
Secondary outcomes (1)
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.
Measured: at least every 3 weeks for a maximum of 30 post coming off drug, approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2013 (estimated)
- Study startMay 2013
- Primary completionNov 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GBMStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heinrich Elinzano, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Progenics Pharmaceuticals, Inc., Rhode Island Hospital, University of Texas
- Responsible party
- Sponsor-investigator, Heinrich Elinzano, MD, Brown University
- Investigators
- Heinrich Elinzano, MD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01856933
- Sponsor's protocol ID
- 263
- Status last verified
- Nov 2021
- First submitted
- 8 Jan 2013
- Last updated
- 23 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study
- ClinicalTrials.gov ID
- NCT01856933
- Acronym / sponsor ID
- 263
- Conditions
- GBM, Glioblastoma Multiforme, Gliosarcoma
- Keywords
- GBM, Glioblastoma Multiforme, Gliosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Heinrich Elinzano, MDUniversity, hospital or other
- Collaborators
- Progenics Pharmaceuticals, Inc., Rhode Island Hospital, University of Texas
- Study start
- May 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 20 May 2013 (estimated)
- Results
- Posted 17 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PSMA ADC | Experimental | Drug: PSMA ADC2.5 mg/kg, IV, over 60 minutes every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (11 listed)
- Non-GBM primary invasive malignant neoplasm within the five years prior to screening except for:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PSMA ADC2.5 mg/kg, IV, over 60 minutes every 3 weeks | Drug | PSMA ADC |
Primary outcome
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
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).
1 secondary outcome
Number of Patients Who Experienced Toxicities (Adverse Events) Who Received PSMA ADC for Recurrent Glioblastoma.
Time frame: at least every 3 weeks for a maximum of 30 post coming off drug, approximately 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heinrich Elinzano, MD principal investigator
Brown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PSMA ADC in people with GBM and Glioblastoma Multiforme, run by Heinrich Elinzano, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.