- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02876003
Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma
February 22, 2017 updated by: GenSpera, Inc.
An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy, Safety and CNS Exposure of G-202 in Patients With PSMA Positive Recurrent or Progressive Glioblastoma
Glioblastoma (GBM) comprises about 16% of all malignancies of the nervous system and over 50% of all gliomas.
Standard of care for newly-diagnosed GBM is a combination of surgical debulking followed by concurrent radiotherapy and chemotherapy with temozolomide.
Efforts to improve second-line therapy in GBM have met with only marginal success and there is a large unmet medical need for new therapies.
G-202 (mipsagargin) is an example of prodrug chemotherapy.
It is activated by Prostate Specific Membrane Antigen (PSMA), which is expressed by some cancer cells and in the blood vessels of most solid tumors, including GBM, but not by normal cells or blood vessels in normal tissue.
It is believed that activation of the prodrug G-202 will allow the drug to kill cancer cells.
This study will evaluate the activity, safety and CNS exposure of G-202 in patients with PSMA-positive recurrent or progressive GMB receiving G-202 by intravenous infusion on three consecutive days of a 28-day cycle.
Study Overview
Study Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Santa Monica, California, United States, 90404
- John Wayne Cancer Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Written informed consent to participate in this study
- Histological or radiological confirmation of glioblastoma with PSMA positivity
- Recurrent or progressive GBM following at least one (1), but no more than two (2) prior regimens; one of the prior regimens must have included surgery and/or radiotherapy
- Age >/= 18 years
- Karnofsky Performance Status (KPS) ≥ 60%
- Life expectancy > 2 months
- Adequate hematologic, renal and hepatic function
- Adequate coagulation profile
- Not pregnant, nursing or planning to become pregnant; willing to use contraception
Exclusion Criteria:
- Deteriorating neurological symptoms, or need for increasing doses of corticosteroids or new onset of seizures
- Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1 week of first G-202 treatment
- Toxicity from prior therapy (excluding alopecia) that has not resolved to ≤ Grade 1 unless otherwise specified
- Investigational or cytotoxic therapy within 28 days or nitrosoureas within 42 days of the first treatment with G-202
- Currently requiring any type of full-dose anti-coagulation treatment, systemic administration of antibiotics or chronic administration of anti-viral agents.
- History or evidence of cardiac risk, including QTc interval on screening ECG >470 msec, left ventricular ejection fraction (LVEF) < 50%, clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia, history of acute coronary syndromes within 6 months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary artery bypass graft, angioplasty, or stenting)
- Uncontrolled cardiac or coronary artery disease
- Uncontrolled hypertension (mean systolic BP ≥ 160 mm Hg and/or mean diastolic BP ≥ 100 mm Hg on 3 determinations 5 minutes apart while on 2 anti-hypertensive agents) or hypertension requiring treatment with more than 2 anti-hypertensive agents
- Severe or uncontrolled medical disease, including uncontrolled diabetes, congestive heart failure, chronic renal disease or chronic pulmonary disease
- Severe GI bleeding within 12 weeks of treatment with G-202
- Known history of HIV, hepatitis B or hepatitis C
- Documentation of keratosis follicularis (also known as Darier or Darier-White disease)
- Requirement for chronic use of strong inhibitors or inducers of cytochrome (CYP3A4) iso-enzymes
- Known hypersensitivity to any study drug component including thapsigargin derivatives, polysorbate 20, or propylene glycol
- Any other condition, including concurrent medical condition, social circumstance or drug dependency, which in the opinion of the investigator could compromise patient safety and/or compliance with study requirements
- Another primary malignancy that has not been in remission for at least 2 years; non-melanoma skin cancer, intraepithelial carcinoma of the cervix, or prostate cancer with a current PSA ≤ 0.1 ng/mL is allowed-
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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: G-202 (Mipsagargin)
G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle
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G-202 administered by intravenous infusion (IV, in the vein) on Days 1, 2 and 3 of each 28-day cycle until progression or development of unacceptable toxicity
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
6-month progression-free survival
Time Frame: 6 months
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Percentage of patients who received at least 2 cycles of G-202 and have not progressed, according to criteria of the Response Assessment in Neuro-Oncology Working Group (RANO), or died within 6 months of beginning treatment with G-202
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: Every 2 weeks for approximately 1 year
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Proportion of patients experiencing treatment-emergent adverse events
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Every 2 weeks for approximately 1 year
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Objective tumor response rate, best overall response
Time Frame: Every 8 weeks for approximately one year
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Response rate assessed by RANO criteria
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Every 8 weeks for approximately one year
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Duration of PFS
Time Frame: Every 4 weeks for approximately one year
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Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months
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Every 4 weeks for approximately one year
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Overall survival
Time Frame: Every 4 weeks for approximately one year
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Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months
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Every 4 weeks for approximately one year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Garni Barkhoudarian, M.D., Saint John's Cancer Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2016
Primary Completion (Anticipated)
October 1, 2019
Study Completion (Anticipated)
October 1, 2020
Study Registration Dates
First Submitted
August 18, 2016
First Submitted That Met QC Criteria
August 18, 2016
First Posted (Estimate)
August 23, 2016
Study Record Updates
Last Update Posted (Actual)
February 24, 2017
Last Update Submitted That Met QC Criteria
February 22, 2017
Last Verified
February 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- G-202-008
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
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.
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