Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma
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|ClinicalTrials.gov Identifier: NCT03027388|
Recruitment Status : Recruiting
First Posted : January 23, 2017
Last Update Posted : June 2, 2023
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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.
To see if LB100 can pass into the brain.
People at least 18 years old with a brain tumor that requires surgery
Participants will be screened with:
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.
|Condition or disease||Intervention/treatment||Phase|
|Astrocytoma, Grades II, III and IV Glioblastoma Multiforme Giant Cell Glioblastoma Glioma Oligodendrogliomas||Drug: LB-100||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Phase II Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma|
|Actual Study Start Date :||January 9, 2019|
|Estimated Primary Completion Date :||August 31, 2023|
|Estimated Study Completion Date :||August 31, 2023|
Treatment with LB100
LB-100 will be infused over 2 hours via IV infusion 2 to 4 hours before surgery. The dose established from a Phase I study will be 2.33 mg/m2.
- Drug Level in tumor tissue [ Time Frame: Post Surgery ]To determine the pharmacokinetic properties of LB100 in glioblastoma tumor tissues
- Relationship between drug concentration at the site of action and the resulting effect and the presence of correlation to identify predictive markers. [ Time Frame: 8 hours post infusion ]Intra-patient PD effect in PBMC and tumor tissue will be evaluated in all subjects for presence of correlation to identify potential predictive markers
- Plasma concentration and calculated LB100 [ Time Frame: 8 hours post infusion ]determine the plasma concentration and calculated PK parameters of LB100 and LB100M (endothall).
- Concentration of LG100 and its major metabolite LB100 in glioblastoma tumor tissue [ Time Frame: 8 hours post infusion ]determine the concentration LB100 and its major metabolite, 7-oxabicyclo [2.2.1] heptanes-2,3-dicarboxylic acid (LB100M) in glioma tumor tissue when a known non-toxic dose of LB100 is delivered intravenously over 2 hours
- Changes in phospho-protein expression in circulating PBMC [ Time Frame: 8 hours post infusion ]determine changes in phospho-protein expression in circulating PBMC
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 (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 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.
- 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.
- Known 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 by the Neuro-Oncology Branch, Clinical Center. This study will be posted on NIH websites and on NIH Social media forums.
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): NCT03027388
|Contact: NCI NOB Referral Group||(866) firstname.lastname@example.org|
|Contact: Eric C Burton, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Eric C Burton, M.D.||National Cancer Institute (NCI)|
|Responsible Party:||National Cancer Institute (NCI)|
|Other Study ID Numbers:||
|First Posted:||January 23, 2017 Key Record Dates|
|Last Update Posted:||June 2, 2023|
|Last Verified:||January 30, 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||.BTRIS: All IPD recorded in the medical record will be shared with intramural investigators upon request.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
|Time Frame:||BTRIS: Clinical data available during the study and indefinitely.|
|Access Criteria:||BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Blood Brain Barrier
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Molecular Mechanisms of Pharmacological Action