- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01856933
BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)
BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
-
-
Texas
-
Dallas, Texas, United States, 75235
- UT Southwestern
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PSMA ADC
2.5 mg/kg, IV, over 60 minutes every 3 weeks
|
2.5 mg/kg, IV, over 60 minutes every 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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). |
3 months until progression, potentially up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Please note that toxicities outlined may not all be related to the treatment regimen.
|
at least every 3 weeks for a maximum of 30 post coming off drug, approximately 6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heinrich Elinzano, MD, Brown University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 263
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Glioblastoma Multiforme
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States, Belgium, Switzerland, Germany, Netherlands
-
Milton S. Hershey Medical CenterRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
-
Milton S. Hershey Medical CenterNational Cancer Institute (NCI)RecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Recurrent Glioblastoma | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of Brain | Astrocytoma of Brain | Astrocytoma, MalignantUnited States, Germany, Netherlands, Switzerland, Belgium
-
Leland MethenyNational Cancer Institute (NCI)RecruitingGlioblastoma Multiforme | Supratentorial Gliosarcoma | Glioblastoma Multiforme, Adult | Supratentorial GlioblastomaUnited States
-
University of UtahWithdrawnGlioblastoma Multiforme (GBM)United States
-
Sunnybrook Health Sciences CentreRecruitingGlioblastoma Multiforme, AdultCanada
-
Hebei Senlang Biotechnology Inc., Ltd.RecruitingGlioblastoma Multiforme, AdultChina
-
Polaris GroupRecruitingGlioblastoma Multiforme (GBM)Taiwan
-
University of IowaEisai Inc.TerminatedPrimary Glioblastoma MultiformeUnited States
Clinical Trials on PSMA ADC
-
Progenics Pharmaceuticals, Inc.Completed
-
Progenics Pharmaceuticals, Inc.CompletedProstate CancerUnited States
-
Progenics Pharmaceuticals, Inc.CompletedProstate CancerUnited States
-
Progenics Pharmaceuticals, Inc.CompletedProstate CancerUnited States
-
Shanghai General Hospital, Shanghai Jiao Tong University...NanoMab Technology (UK) LimitedCompleted
-
Irene BurgerCompletedProstate CancerSwitzerland
-
Norwegian University of Science and TechnologyUniversity Hospital of North Norway; Haukeland University Hospital; St. Olavs...RecruitingProstatic Neoplasms | Neoplasm MetastasisNorway
-
Cancer Institute and Hospital, Chinese Academy...RecruitingMetastatic Breast CancerChina
-
Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co...RecruitingRefractory or Recurrent CD30+ Hematologic MalignanciesChina
-
RemeGen Co., Ltd.Completed