Trial Outcomes & Findings for Brain Interstitium Temozolomide Concentration Pre and Post Regadenoson Administration (NCT NCT02389738)

Results Overview

The AUC-T for each day will be estimated by the trapezoid rule, based on the number of time points available for the particular evaluable patient. The PK variables will be tabulated and descriptive statistics calculated pre and post Regadenoson. The difference of AUCs will be summarized by mean and standard deviation or median and range if there is large variation from patient to patient. Means and standard deviation or mean and range will be presented for Cmax and AUC(inf) for each group. Graphic method will be used to display the difference for individual patient and all five patients.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

6 participants

Primary outcome timeframe

18 hours post temozolomide administration

Results posted on

2018-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	BBB Disruption With Regadenoson This is an exploratory (pilot) study to assess whether Regadenoson can disrupt the BBB, change the barrier permeability, to enhance the temozolomide delivery to brain. Five evaluable patients will be studied in this trial. The sample size justification is not based on statistical rationale but clinical affordability. If the investigators detect ≥ 50% increase in temozolomide brain interstitium concentrations after Regadenoson, then the investigators will consider future studies evaluating additional patients. Regadenoson: Regadenoson administration on post-op day 2 after temozolomide administration. Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration. Temozolomide: Temozolomide administration on post-op day 1 and 2. Microdialysis catheter: Microdialysis catheter placement post surgical resection Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration.
Overall Study STARTED	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Brain Interstitium Temozolomide Concentration Pre and Post Regadenoson Administration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BBB Disruption With Regadenoson n=6 Participants This is an exploratory (pilot) study to assess whether Regadenoson can disrupt the BBB, change the barrier permeability, to enhance the temozolomide delivery to brain. Five evaluable patients will be studied in this trial. If the investigators detect ≥ 50% increase in temozolomide brain interstitium concentrations after Regadenoson, then the investigators will consider future studies evaluating additional patients. Regadenoson: Regadenoson administration on post-op day 2 after temozolomide administration. Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration. Temozolomide: Temozolomide administration on post-op day 1 and 2. Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration. Microdialysis catheter: Microdialysis catheter placement post surgical resection and removed at the bedside after completion of obtaining all dialysate collections.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=99 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants
Age, Continuous	51 years n=99 Participants
Sex: Female, Male Female	1 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Region of Enrollment United States	6 Participants n=99 Participants

PRIMARY outcome

Timeframe: 18 hours post temozolomide administration

The AUC-T for each day will be estimated by the trapezoid rule, based on the number of time points available for the particular evaluable patient. The PK variables will be tabulated and descriptive statistics calculated pre and post Regadenoson. The difference of AUCs will be summarized by mean and standard deviation or median and range if there is large variation from patient to patient. Means and standard deviation or mean and range will be presented for Cmax and AUC(inf) for each group. Graphic method will be used to display the difference for individual patient and all five patients.

Outcome measures

Outcome measures
Measure	BBB Disruption With Regadenoson n=5 Participants This is an exploratory (pilot) study to assess whether Regadenoson can disrupt the BBB, change the barrier permeability, to enhance the temozolomide delivery to brain. Five evaluable patients will be studied in this trial. The sample size justification is not based on statistical rationale but clinical affordability. If the investigators detect ≥ 50% increase in temozolomide brain interstitium concentrations after Regadenoson, then the investigators will consider future studies evaluating additional patients. Regadenoson: Regadenoson administration on post-op day 2 after temozolomide administration. Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration. Temozolomide: Temozolomide administration on post-op day 1 and 2. Microdialysis catheter: Microdialysis catheter placement post surgical resection. Temozolomide plasma and dialysate concentrations will be obtained over 18 hours post temozolomde administration.
Change in AUC0-18 of the Temozolomide Concentration (AUC-T) in Brain Interstitium Before and After Regadenoson Infusion Temozolomide alone AUC brain/plasma	19.1 percentage of AUC Interval 3.3 to 31.5
Change in AUC0-18 of the Temozolomide Concentration (AUC-T) in Brain Interstitium Before and After Regadenoson Infusion Temozolomide/Regadenoson AUC brain/plasma	18.0 percentage of AUC Interval 7.5 to 27.5

SECONDARY outcome

Timeframe: 24 hours post-op

The study of collecting biochemical markers of glioma with correlation to current or past cognitive/mood disorders with Montgomery-Asberg. Biomarkers will be obtained post-op day 1 from dialysate collections and later identified and quantified.

Outcome measures

Outcome data not reported

Adverse Events

BBB Disruption With Regadenoson

Serious events: 0 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Principal Investigator

Johns Hopkins/NIH

Phone: 4109558837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place