Trial Outcomes & Findings for Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma (NCT NCT03027388)

NCT ID: NCT03027388

Last Updated: 2023-11-22

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: an average of 5.5 hours after drug administration
• Results posted on: 2023-11-22

Participant Flow

Participant milestones

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma Treatment with LB100 LB-100: 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.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

Baseline characteristics by cohort

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=7 Participants Treatment with LB100 LB-100: 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	57.17 years STANDARD_DEVIATION 7.54 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: an average of 5.5 hours after drug administration

Population: 2/7 were not analyzed because no tumor was found on analysis.

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

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Number of Participants With the Presence of Drug in the Tumor Tissue	2 Participants

SECONDARY outcome

Timeframe: 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

Blood samples for the determination of plasma levels of LB-100 will be obtained from each participant. Plasma concentrations of LB100 will be determined at each time point. LC-MS-MS assay that can measure LB-100 in human plasma. Assay range is 2.0 -1000 ng/mL. A higher value is better because it would have made it more likely drug could penetrate the blood brain barrier at therapeutic levels.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Plasma Concentration and Calculated LB100 Pre-dose	0.0 (rounded)nM Interval 0.0 to 0.0
Plasma Concentration and Calculated LB100 End of infusion (2 hours post-start)	575 (rounded)nM Interval 354.0 to 772.0
Plasma Concentration and Calculated LB100 30 minutes post LB100 infusion completion	534 (rounded)nM Interval 291.0 to 626.0
Plasma Concentration and Calculated LB100 1 hour post LB-100 infusion completion	355 (rounded)nM Interval 251.0 to 633.0
Plasma Concentration and Calculated LB100 2 hours post LB100 infusion completion	192 (rounded)nM Interval 174.0 to 263.0
Plasma Concentration and Calculated LB100 4 hours post LB100 infusion completion	80 (rounded)nM Interval 30.0 to 150.0
Plasma Concentration and Calculated LB100 8 hours post LB100 infusion completion	16 (rounded)nM Interval 7.0 to 71.0

SECONDARY outcome

Timeframe: average of 5.5 hours after infusion

Concentration of LB100 in glioma tumor tissue when a known non-toxic dose of LB100 is delivered intravenously. Glioma tissue sampling to detect and quantify LB100 will be performed by assaying phospho-protein expression in glioma tissue resected prior to and after infusion of LB100. These are values for the LB100 in the tumor which was done at one timepoint.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Concentration of LB100	0.18 nM Interval 0.0 to 0.67

SECONDARY outcome

Timeframe: 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

Population: Data was not collected.

Changes in phospho-protein expression in circulating PBMC. Pharmacodynamic (PD) response is defined as statistically significant elevation of phospho-protein expression in treated tumor tissues compared to untreated glioma specimens. Post-treatment PD effect (as measured by increase in tumor tissue phospho-protein expression) difference greater than 2.5 times the baseline standard deviation (SD) is statistically significant at the .05 significance level.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

The maximum observed analyte concentration in serum was reported.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Maximum Observed Plasma Concentration of LB100 (Cmax)	156 ng/mL Interval 95.0 to 207.0

SECONDARY outcome

Timeframe: 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

AUC is a measure of the serum concentration of LMB100 over time. It is used to characterize drug absorption.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)	438 hr*ng/mL Interval 319.0 to 585.0

SECONDARY outcome

Timeframe: 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

Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Plasma Half-Life of Drug LB100	1.20 Hours Interval 1.09 to 1.46

SECONDARY outcome

Timeframe: 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

Time to maximum observed plasma concentration of LMB100 (Tmax).

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Time to Maximum Observed Plasma Concentration of LMB100 (Tmax)	2.10 Hours Interval 2.0 to 2.63

SECONDARY outcome

Timeframe: 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

The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Total Clearance (CL) of LMB100	10.4 L/hr Interval 7.13 to 14.7

SECONDARY outcome

Timeframe: 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

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Volume of Distribution (Vd) of LMB100	20.1 L Interval 12.2 to 31.3

SECONDARY outcome

Timeframe: 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

Drug amount in brain as a percent of drug in plasma.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Brain Concentration	0.30 percent Interval 0.0 to 0.45

SECONDARY outcome

Timeframe: 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 drug in brain tumor tissue. Brain penetration is measured as "drug amount in a brain as a percent of drug in plasma.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=5 Participants Treatment with LB100 LB-100: 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.
Brain Penetration	0.26 Percent Interval 0.0 to 0.7

OTHER_PRE_SPECIFIED outcome

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

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=7 Participants Treatment with LB100 LB-100: 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.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	7 Participants

Adverse Events

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

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=7 participants at risk Treatment with LB100 LB-100: 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.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
General disorders Fever	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Musculoskeletal and connective tissue disorders Myalgia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.

Other adverse events

Measure	1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma n=7 participants at risk Treatment with LB100 LB-100: 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.
Psychiatric disorders Agitation	28.6% 2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Nervous system disorders Dysphasia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, impacted cerumen	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Ear and labyrinth disorders Ear pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Nervous system disorders Facial muscle weakness	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Nervous system disorders Headache	71.4% 5/7 • Number of events 7 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Respiratory, thoracic and mediastinal disorders Hiccups	28.6% 2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Metabolism and nutrition disorders Hypocalcemia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Metabolism and nutrition disorders Hypomagnesemia	28.6% 2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Metabolism and nutrition disorders Hypophosphatemia	42.9% 3/7 • Number of events 3 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Nervous system disorders Muscle weakness left-sided	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Investigations Platelet count decreased	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.
Skin and subcutaneous tissue disorders Skin induration	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 39 months and 6 days.

Additional Information

Dr. Eric Burton

National Cancer Institute

Phone: 240-760-6436

Email: eric.burton@nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place