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

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ClinicalTrials.gov Identifier: NCT02067156
Recruitment Status : Completed
First Posted : February 20, 2014
Last Update Posted : February 24, 2017
Sponsor:
Information provided by (Responsible Party):
GenSpera, Inc.

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 recurrent or progressive GMB receiving G-202 by intravenous infusion on three consecutive days of a 28-day cycle. Funding Source - FDA OOPD

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: G-202 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma
Study Start Date : February 2014
Actual Primary Completion Date : December 2016
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: G-202 (Mipsagargin)
G-202 (Mipsagargin) administered by intravenous infusion on 3 consecutive days of a 28-day cycle
Drug: 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




Primary Outcome Measures :
  1. 6-month progression-free survival [ Time Frame: 6 months ]
    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 :
  1. Safety [ Time Frame: Every 2 weeks for approximately one year ]
    Proportion of patients experiencing treatment-emergent adverse events

  2. Objective tumor response rate, best overall response [ Time Frame: Every 8 weeks for approximately one year ]
    Response rate assessed by RANO criteria

  3. Duration of PFS [ Time Frame: Every 4 weeks for approximately one year ]
    Duration of time from the first administration of G-202 until the first documented progression or date of death, assessed up to 12 months

  4. Overall survival [ Time Frame: Every 4 weeks for approximately one year ]
    Duration of time from the first administration of G-202 until the date of death, assessed up to 12 months

  5. G-202 pharmacokinetics and pharmacodynamics [ Time Frame: Within 4 weeks of receiving G-202 ]
    G-202 levels in CSF and serum; biomarkers in CSF, tumor and serum



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02067156


Locations
United States, California
University of California, San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
GenSpera, Inc.
Investigators
Principal Investigator: David Piccioni, M.D., Ph.D. University of California, San Diego Moores Cancer Center

Responsible Party: GenSpera, Inc.
ClinicalTrials.gov Identifier: NCT02067156     History of Changes
Other Study ID Numbers: G-202-004
R01FD005077 ( U.S. FDA Grant/Contract )
First Posted: February 20, 2014    Key Record Dates
Last Update Posted: February 24, 2017
Last Verified: February 2017

Keywords provided by GenSpera, Inc.:
glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue