Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

• Status: Enrolling by invitation
• Trial end date: 2023-08-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: LB100

Criteria

• INCLUSION CRITERIA:

• Patients must have histologically confirmed glioblastoma/gliosarcoma, grades II-III astrocytoma and oligodendroglioma confirmed by the Laboratory of Pathology, NCI.

• 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 (WBC greater than or equal to 3,000/uL 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 ULN). These tests must be performed within 14 days prior to registration. 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 registration. (*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.

• Tumor tissue blocks or at least 20 unstained slides from a prior diagnosis will be requested. H&E to confirm diagnosis must be available. The 20 unstained slides is preferred, but not required.

• 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 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.

• 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 CYP450 inducers or inhibitors are ineligible

• Recruitment Strategies

Patients with recurrent disease will be identified at the Outpatient Clinic of the Neuro-Oncology Branch, Clinical Center.