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Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma

Primary Purpose

Glioblastoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
G-202
Sponsored by
GenSpera, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

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

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-

Sites / Locations

  • John Wayne Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

G-202 (Mipsagargin)

Arm Description

G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle

Outcomes

Primary Outcome Measures

6-month progression-free survival
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

Secondary Outcome Measures

Safety
Proportion of patients experiencing treatment-emergent adverse events
Objective tumor response rate, best overall response
Response rate assessed by RANO criteria
Duration of PFS
Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months
Overall survival
Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months

Full Information

First Posted
August 18, 2016
Last Updated
February 22, 2017
Sponsor
GenSpera, Inc.
Collaborators
Saint John's Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02876003
Brief Title
Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Withdrawn
Why Stopped
This study has been withdrawn prior to enrollment.
Study Start Date
September 2016 (undefined)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
October 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GenSpera, Inc.
Collaborators
Saint John's Cancer Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
G-202 (Mipsagargin)
Arm Type
Experimental
Arm Description
G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle
Intervention Type
Drug
Intervention Name(s)
G-202
Other Intervention Name(s)
Mipsagargin
Intervention Description
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
Primary Outcome Measure Information:
Title
6-month progression-free survival
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Safety
Description
Proportion of patients experiencing treatment-emergent adverse events
Time Frame
Every 2 weeks for approximately 1 year
Title
Objective tumor response rate, best overall response
Description
Response rate assessed by RANO criteria
Time Frame
Every 8 weeks for approximately one year
Title
Duration of PFS
Description
Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months
Time Frame
Every 4 weeks for approximately one year
Title
Overall survival
Description
Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months
Time Frame
Every 4 weeks for approximately one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Garni Barkhoudarian, M.D.
Organizational Affiliation
Saint John's Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
John Wayne Cancer Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma

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