Trial Outcomes & Findings for NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery (NCT NCT03020017)
NCT ID: NCT03020017
Last Updated: 2022-08-26
Results Overview
To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal
COMPLETED
EARLY_PHASE1
8 participants
Up to 21 days after study drug administration
2022-08-26
Participant Flow
Participant milestones
| Measure |
NU-0129 Treatment
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
NU-0129
STARTED
|
8
|
|
NU-0129
COMPLETED
|
8
|
|
NU-0129
NOT COMPLETED
|
0
|
|
Standard of Care Resection
STARTED
|
8
|
|
Standard of Care Resection
COMPLETED
|
8
|
|
Standard of Care Resection
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery
Baseline characteristics by cohort
| Measure |
NU-0129 Treatment
n=8 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Age, Continuous
|
55.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 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
|
1 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
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 21 days after study drug administrationTo evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal
Outcome measures
| Measure |
NU-0129 Treatment
n=8 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Number of Patients With Adverse Events
Experienced any AE
|
8 Participants
|
|
Number of Patients With Adverse Events
Experienced an AE related to NU-01289
|
4 Participants
|
|
Number of Patients With Adverse Events
Experienced any SAE
|
1 Participants
|
|
Number of Patients With Adverse Events
Experienced an SAE related to NU-0129
|
0 Participants
|
SECONDARY outcome
Timeframe: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusionBlood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
Outcome measures
| Measure |
NU-0129 Treatment
n=8 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration
Au maximum observed plasma concentration
|
4290 ng/ml
Interval 3120.0 to 7140.0
|
|
NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration
siRNA maximum observed plasma concentration
|
62.1 ng/ml
Interval 22.8 to 123.0
|
SECONDARY outcome
Timeframe: At time of surgeryPopulation: 2 patients tumor resections resulted in insufficient amount of viable tumor tissue for ICP-MS analysis and were not included in this analysis
Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H\&E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.
Outcome measures
| Measure |
NU-0129 Treatment
n=6 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Biodistribution of NU-0129 in Tumor Tissue
|
20.5 percentage of gold "Au"
Standard Deviation 8.15
|
SECONDARY outcome
Timeframe: At time of infusion (8-48 hours prior to resection) and during surgeryPopulation: Patients who had drug infused and underwent subsequent resection
Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.
Outcome measures
| Measure |
NU-0129 Treatment
n=8 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Feasibility of Giving NU-0129 as a Standard Treatment
Number of patients who had drug infused successfully
|
8 Participants
|
|
Feasibility of Giving NU-0129 as a Standard Treatment
Number of patient who underwent subsequent resection
|
8 Participants
|
SECONDARY outcome
Timeframe: At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusionBlood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.
Outcome measures
| Measure |
NU-0129 Treatment
n=8 Participants
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
NU-0129 Concentration in Blood After Drug Administration Using Half-life
siRNA half-life
|
0.06 hours
Interval 0.02 to 0.16
|
|
NU-0129 Concentration in Blood After Drug Administration Using Half-life
Au half-life
|
18 hours
Interval 12.0 to 23.0
|
Adverse Events
NU-0129 Treatment
Serious adverse events
| Measure |
NU-0129 Treatment
n=8 participants at risk
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Nervous system disorders
Cerebrospinal fluid leakage
|
12.5%
1/8 • Number of events 1 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
Other adverse events
| Measure |
NU-0129 Treatment
n=8 participants at risk
NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.
|
|---|---|
|
Investigations
Alkaline phosphatase increased
|
12.5%
1/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
|
Investigations
Lymphocyte count decreased
|
25.0%
2/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
|
Investigations
Platelet count decreased
|
12.5%
1/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
|
Investigations
White blood cell decreased
|
12.5%
1/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
25.0%
2/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
|
Vascular disorders
Hypertension
|
12.5%
1/8 • Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place