Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma

NCT ID: NCT02067156

Last Updated: 2024-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2017-02-28

Brief Summary

This study will evaluate if a drug called G-202 can be safely used to treat people with glioblastoma (GBM) that has progressed or recurred. G-202 is given by intravenous infusion on three consecutive days of a 28-day cycle.

Detailed Description

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 participants with recurrent or progressive GBM receiving G-202 by intravenous infusion on three consecutive days of a 28-day cycle. Funding Source - FDA Office of Orphan Products Development (OOPD)

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

G-202 (Mipsagargin)

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

Group Type: EXPERIMENTAL

G-202

Intervention Type: DRUG

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

Interventions

G-202

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

Intervention Type: DRUG

Other Intervention Names

Mipsagargin

Eligibility Criteria

Inclusion Criteria

• Written informed consent to participate in this study
• Histological or radiological confirmation of glioblastoma
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

GenSpera, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Piccioni, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego Moores Cancer Center

Locations

University of California, San Diego Moores Cancer Center

La Jolla, California, United States

Countries

United States

Other Identifiers

R01FD005077

Identifier Type: FDA

Identifier Source: secondary_id

View Link

G-202-004

Identifier Type: -

Identifier Source: org_study_id