Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

NCT03027388 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17003717-C-0037
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Astrocytoma, Grades II, III and IV; Glioblastoma Multiforme; Giant Cell Glioblastoma; Glioma; Oligodendrogliomas

Keywords

Brain Tumor; Blood Brain Barrier; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Number of Participants With the Presence of Drug in the Tumor Tissue

  Participants tumor tissue was examined to determine the presence of drug in the tumor tissue.

  an average of 5.5 hours after drug administration

Secondary Outcomes (11)

• Plasma Concentration and Calculated LB100

  Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion

• Concentration of LB100

  average of 5.5 hours after infusion

• Changes in Phospho-protein Expression in Circulating Peripheral Blood Mononuclear Cells (PBMC)

  Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion

• Maximum Observed Plasma Concentration of LB100 (Cmax)

  Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion

• Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)

  Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 39 months and 6 days.

Study Arms (1)

1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

EXPERIMENTAL

Treatment with LB100

Drug: LB-100

Interventions

LB-100 DRUG

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.

1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Glioma; Oligodendroglioma; Brain Neoplasms

Interventions

LB100

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Dr. Eric Burton
• Organization: National Cancer Institute

eric.burton@nih.gov

240-760-6436

Study Officials

• Eric C Burton, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 23, 2017
• Study Start: January 9, 2019
• Primary Completion: August 15, 2022
• Study Completion: August 31, 2022
• Last Updated: November 22, 2023
• Results First Posted: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)