Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma
Condition: Astrocytoma, Grades II, III and IV; Glioblastoma Multiforme; Giant Cell Glioblastoma; Glioma; Oligodendrogliomas
MeSH terms: Glioblastoma; Astrocytoma; Oligodendroglioma
Intervention: LB-100
Intervention description: LB-100 will be infused over 2 hours via intravenous (IV) infusion 2 to 4 hours before surgery. The dose established from a Phase I study will be 2.33 mg/m^2.
Intervention MeSH terms: LB100
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Tumor; Blood Brain Barrier; Pharmacokinetics; Pharmacodynamics

Summary:

      Background:

      The brain is separated from the rest of the blood stream by the blood-brain barrier. This is
      like a filter that protects the brain. But is also a challenge when medicines need to get
      into the brain. Researchers want to give the new drug LB100 to people before brain tumor
      surgery. They will measure how much LB100 is in the blood and how much gets into the brain.
      This may help with the use of LB100 to treat brain tumors in the future.

      Objective:

      To see if LB100 can pass into the brain.

      Eligibility:

      People at least 18 years old with a brain tumor that requires surgery.

      Design:

      Participants will be screened with:

      Physical exam

      Medical history

      Blood tests

      Neurosurgery evaluation

      Scans

      Heart tests

      Tumor sample. This can be from a previous procedure.

      Participants will have their brain surgery at the Clinical Center.

      Participants will get a dose of the study drug through a plastic tube in a vein for 2 hours
      during surgery.

      Participants will have blood taken 7 times in the 8 hours after getting the study drug.

      Tumor samples will be taken during surgery.

      Participants will have a heart test after getting the study drug. Sticky pads on the skin
      will measure electrical activity of the heart.

      Two-three weeks after leaving the hospital, participants will have a follow-up visit. They
      will have a physical exam and blood tests.

      One month after surgery, they will be contacted in person or by phone to see how they are
      doing.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically confirmed glioblastoma/gliosarcoma, grades II-III
             astrocytoma and oligodendroglioma.

          -  Patients must have recurrent disease for which there is a clinical indication for
             resection.

          -  Age greater than or equal to18 years.

          -  Karnofsky greater than or equal to 60%.

          -  Patients must have adequate bone marrow function (white blood count (WBC) greater than
             or equal to 3,000/uL absolute neutrophil count (ANC) greater than or equal to
             1,500/mm^3, platelet count of greater than or equal to 100,000/mm^3, and hemoglobin
             greater than or equal to 10 gm/dL), adequate liver function (SGOT and bilirubin < 2
             times upper limit of normal (ULN). These tests must be performed within 28 days prior
             to receiving drug. Eligibility level for hemoglobin may be reached by transfusion.

          -  Patients must have a serum creatinine of <=1.7 mg/dL. If the serum creatinine is
             greater than 1.7 mg/dl, a 24-hour urine creatinine clearance will be obtained and if
             the result of this study is within normal limits*, the patient would be eligible to
             enroll onto study. This test must be performed within 28 days prior to
             registrationreceiving drug. (*Normal Creatinine Clearance Range: Male: 90 - 130
             ml/min; Female: 80 - 125 ml/min)

          -  Patients must be in adequate general medical health to safely tolerate a craniotomy.

          -  At the time of registration, all subjects must be removed greater than or equal to 28
             days from any investigational agents.

          -  The effects of LB100 on the developing human fetus are unknown. For this reason, women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document indicating that they are aware of the investigational nature of this
             study, and that this is not a therapeutic clinical trial.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients unwilling to undergo craniotomy.

          -  Pregnant women are excluded from this study because the safety of Protein Phosphatase
             2A (PP2A) inhibition on a developing fetus has not been established. Because there is
             an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with LB100, breastfeeding should be discontinued if the mother
             is treated with LB100.

          -  Patients may not have had prior chemotherapy or biologic therapy in the 4 weeks prior
             to study entry. For patients who have been treated with targeted therapy, 5 half-lives
             of that therapy (or 28 days, whichever is shorter) must have passed prior to
             enrollment in the study.

          -  Known human immunodeficiency virus (HIV)-positive patients on combination
             antiretroviral therapy are ineligible because of the potential for pharmacokinetic
             interactions with LB100. Appropriate studies will be undertaken in patients receiving
             combination antiretroviral therapy when indicated.

          -  Patients who are receiving strong cytochromes P450 (CYP450) inducers or inhibitors are
             ineligible

          -  Recruitment Strategies

        Patients with recurrent disease will be identified by the Neuro-Oncology Branch, Clinical
        Center. This study will be posted on National Institutes of Health (NIH) websites and on
        NIH Social media forums.