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Trial record 88 of 107 for:    PHENYTOIN

Tetra-O-Methyl Nordihydroguaiaretic Acid in Treating Patients With Recurrent High-Grade Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00404248
Recruitment Status : Completed
First Posted : November 28, 2006
Results First Posted : August 11, 2015
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Drug: terameprocol
Other: pharmacological study
Enrollment 35
Recruitment Details subjects were accrued 2007-2008 in outpatient clinic
Pre-assignment Details  
Arm/Group Title Arm 1 Enzyme Inducing Antiseizure Drug (+ EIASD) Level 1 Arm 2 +EIASD Level 2 Arm 3 +EIASD Level 3 Arm 4 +EIASD Level 4 Arm 5 Non-Enzyme Inducing Antiseizure Drug (-EIASD) Level 1 Arm 6 -EIASD Level 2 Arm 7 -EIASD Level 3 Arm 8 -EIASD Level 4 Arm 9 - Non Stratified (Both +EIASD and -EIASD)
Hide Arm/Group Description

subjects on the +EIASD (Level 1) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 1= 750mg/day. NO intrasubject dose escalation.

Pharmacokinetics (PK) data will be collected on day one of cycle one infusion

subjects on the +EIASD (Level 2) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 2= 1100mg/day. NO intrasubject dose escalation.

subjects on the +EIASD (Level 3) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 3= 1700mg/day. NO intrasubject dose escalation. Includes pts at the new formulation TC6 at 1700mg

subjects on the +EIASD (Level 4) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 4= 2220mg/day. NO intrasubject dose escalation.

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 1 = 750mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 2 = 1100mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 3 = 1700mg/day. NO intrasubject dose escalation. this Arm including pts treated at the new formulation TC6 at 1700mg

PK data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 4 = 2200mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in this group were not stratified based on anti-sezuire medication..

Subjects will take terameprocol for 5 consecutive days each month by IV. This was for dose 2200mg/day. New formulation TC6.

Period Title: Overall Study
Started 3 4 5 2 3 3 6 6 3
Completed 3 3 5 2 3 3 6 6 3
Not Completed 0 1 0 0 0 0 0 0 0
Reason Not Completed
pts declining status             0             1             0             0             0             0             0             0             0
Arm/Group Title Arm 1 +EIASD Arm 2 -EIASD Arm 3 no Stratification (+EIASD or -EIASD) Total
Hide Arm/Group Description

subjects on the +EIASD treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Subjects were not stratified by antiseizure drugs

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Only dose tested: 2200.

NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Total of all reporting groups
Overall Number of Baseline Participants 14 18 3 35
Hide Baseline Analysis Population Description
high grade gliomas (GBM, AA or AO) histologically confirmed
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 14 participants 18 participants 3 participants 35 participants
47
(29 to 67)
45
(33 to 71)
57
(36 to 65)
46
(29 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 18 participants 3 participants 35 participants
Female
7
  50.0%
11
  61.1%
1
  33.3%
19
  54.3%
Male
7
  50.0%
7
  38.9%
2
  66.7%
16
  45.7%
Karnofsky Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 18 participants 3 participants 35 participants
100 2 1 1 4
90 6 7 0 13
80 0 5 0 5
70 4 4 1 9
60 2 1 1 4
[1]
Measure Description: this is a performance assessment, or functional impairment. 100% is a perfect score no impariment (highest score) and 60% Requires occasional assistance, but is able to care for most of his personal needs. You had to have at least a 60% to be eligible fof the study.
Histologic diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 18 participants 3 participants 35 participants
Glioblastoma 5 7 3 15
anaplastic oligodendroglioma 5 5 0 10
anaplastic astrocytoma 4 6 0 10
1.Primary Outcome
Title Maximum Tolerated Dose (Phase I)
Hide Description Using the PEG formulation pts both with and without enzyme inducing antiseizure drugs (EIASD) were treated at Doses 750, 1100, 1700, 2200 mg/day for five days = 28pts Using the PEG free formulation pts with and without EIASD) were treated at 1700 and 2200 mg/day X 5 days = 8pgs
Time Frame first 30 days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 +EIASD (Enzyme-inducing Antizeizure Drug) ARM 2 -EIASD (Enzyme-inducing Antizeizure Drug) ARM 3 (No Stratification)
Hide Arm/Group Description:

subjects on the +EIASD (Level 1) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Various Dose levels 1= 750mg/dayx5; 2=1100mg/dayx5; 3=1700mg/dayx5; 4=2200mg/dayx5

NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Various Dose levels 1= 750mg/dayx5; 2=1100mg/dayx5; 3=1700mg/dayx5; 4=2200mg/dayx5

NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in this group were not stratified based on anti-sezuire medication..

Subjects will take terameprocol for 5 consecutive days each month by IV. This was for dose 2200mg/day.

New formulation TC6.

Overall Number of Participants Analyzed 14 18 3
Measure Type: Number
Unit of Measure: mg/day x 5 days
1700 1700 1700
2.Primary Outcome
Title Maximum Tolerated Dose (Phase I) - Dose Limiting Toxicity (DLT)
Hide Description Dose limiting Toxicity defined as: Treatment related events; absolute neutrophil count </=500 /mm3; platelets count </=25,000/mm3; febrile neutropenia; any grade 3 or 4 non-hematologic toxicity; any delay in starting subsequent course of treatment for >14 days because of incomplete recovery from treatment
Time Frame First 30 days
Hide Outcome Measure Data
Hide Analysis Population Description

+EIASD on hepatic enzyme-inducing drugs; -EIASE not on hepatic enzyme-induzing drug or drugs that significantly induce the hepatic enzyme.

IV Formulations: +PEG; 10mg/mL solution of PEG 300, hydroxypropyl-B-cyclodextrin & water ; -PEG; 6mg/mL, hydroxypropyl-B-cyclodextrin & water - NEW TC6 formulation

Arm/Group Title + EIASD Level 1 (750 mg/dayx5D) +EIASD Level 2 (1100 mg/dayx5D) +EIASD Level 3 (1700 mg/dayx5D) +EIASD Level 4 (2200 mg/dayx5D) -EIASD Level 1 (750 mg/dayx5D) -EIASD Level 2 (1100 mg/dayx5D) -EIASD Level 3 (1700 mg/dayx5D) -EIASD Level 4 (2200 mg/dayx5D) Non Stratified (Both +EIASD and -EIASD)
Hide Arm/Group Description:

subjects on the +EIASD (Level 1) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 1= 750mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

subjects on the +EIASD (Level 2) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 2= 1100mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

subjects on the +EIASD (Level 3) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 3= 1700mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation; Includes patientss at the new formulation TC6 (-PEG)

subjects on the +EIASD (Level 4) treatment arm were taking one of these antiseizure drugs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 4= 2220mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 1 = 750mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 2 = 1100mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 3 = 1700mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation and new TC6 -PEG Formulation - Pts treated from both formulations

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 4 = 2200mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in this group were not stratified based on anti-sezuire medication..

Subjects will take terameprocol for 5 consecutive days each month by IV. This was for dose 2200mg/day.

New formulation TC6 - NONPEG or -PEG. (polyethylene glycol )

Overall Number of Participants Analyzed 3 4 5 2 3 3 6 6 3
Measure Type: Number
Unit of Measure: Dose Limiting Toxicities (DLT)
0 0 0 0 0 0 0 2 2
3.Secondary Outcome
Title Pharmacokinetics - Total Body Clearance
Hide Description

effect of hepatic enzyme-inducing drugs on PKs

Cycle 1 Day 1 of treatment: Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.

Cycle Day 5 of treatment: Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.

Time Frame Cycle 1 Day 1- Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs. and Cycle 1 Day 5 Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.
Hide Outcome Measure Data
Hide Analysis Population Description
No PKs were collected for the three patients who were treated on Arm 3 (all EIASD). Due to incomplete collection of PKs on Cycle 1 Day 5 only the PKs from Cycle 1 Day 1 were used in the analysis
Arm/Group Title Arm 1 +EIASD Arm 2 -EIASD
Hide Arm/Group Description:

subjects on the +EIASD treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Overall Number of Participants Analyzed 9 16
Mean (Standard Deviation)
Unit of Measure: Liters/hour
53.7  (14.6) 54.4  (20.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1 +EIASD, Arm 2 -EIASD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Pharmacokinetics - Steady-State Apparent Volume Distribution
Hide Description

effect of hepatic enzyme-inducing drugs on PKs

Cycle 1 Day 1 of treatment: Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.

Cycle Day 5 of treatment: Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.

Time Frame Cycle 1 Day 1- Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs. and Cycle 1 Day 5 Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.
Hide Outcome Measure Data
Hide Analysis Population Description
no PKs were collected for Arm 3. Due to incomplete collection of PKs on Cycle 1 Day 5 only the PKs from Cycle 1 Day 1 were used in the analysis
Arm/Group Title Arm 1 +EIASD Arm 2 -EIASD
Hide Arm/Group Description:

subjects on the +EIASD treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Overall Number of Participants Analyzed 9 16
Mean (Standard Deviation)
Unit of Measure: Liters
706  (425) 612  (478)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1 +EIASD, Arm 2 -EIASD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Pharmacokinetics - Terminal Phase Half-life
Hide Description effect of hepatic enzyme-inducing drugs on PKs
Time Frame Cycle 1 Day 1- Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs. and Cycle 1 Day 5 Predose: 1hour(hr) prior, 15minutes(min) prior; postdose: 1 hr15 min; 1.5hr, 2, 3,4, 6, 24 hrs.
Hide Outcome Measure Data
Hide Analysis Population Description
no PKs for Arm 3 (All EIASD) were collected. Due to incomplete collection of PKs on Cycle 1 Day 5 only the PKs from Cycle 1 Day 1 were used in the analysis
Arm/Group Title Arm 1 +EIASD Arm 2 -EIASD
Hide Arm/Group Description:

subjects on the +EIASD treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hepatic enzymes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Starting dose is 750mg/day. Dose escalation is 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300. NO intrasubject dose escalation.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Overall Number of Participants Analyzed 9 16
Mean (Standard Deviation)
Unit of Measure: Hour
18.2  (8.8) 17.1  (9.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1 +EIASD, Arm 2 -EIASD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Efficacy - Best Overall Response
Hide Description Response Criteria: Complete Response (CR): complete disappearance of all tumor, off all steroids, stable or improving neuro exam for min of 4wks; Partial Response (PR): Greater than 50% reduction in tumor size, bi-dimensional MRI/CT, stable steroids, stable or improving neuro for min of 4 wks; Progressive Disease (PD): Progressive neurologic abnormalities not explanined by causes unrelated to tumor progression, or 25% increase in size of tumor by MRI/CT scan, or if new lesion appears; Stable Disease (SD): patient whose clinical status and MRI/CT measurements do not meet the criteria for CR, PR or PD.
Time Frame About 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
3 pt did not have proper scans to be evaluable for analysis
Arm/Group Title Phase 1 Terameprocol
Hide Arm/Group Description:

subjects were either on the +EIASD antiseizure durgs: (phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine). or not on antiseizure drugs - or those effecting hepatic enzymes ( -EIASD) such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: participants
Complete Response 0
Partial Response 0
Progressive Disease 23
Stable Disease 9
7.Secondary Outcome
Title Survival
Hide Description Survival measured from first day of treatment to date of death
Time Frame time to death - up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
3 pts still alive at time of analysis
Arm/Group Title Phase 1 Terameprocol
Hide Arm/Group Description:

subjects were either on the +EIASD antiseizure durgs: (phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine). or not on antiseizure drugs - or those effecting hepatic enzymes ( -EIASD) such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

PK (pharmacological study) data will be collected on day one of cycle one infusion

Overall Number of Participants Analyzed 32
Median (Standard Deviation)
Unit of Measure: months
5.5  (8.4)
Time Frame While patients were actively on treatment and for 30 days post treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title + EIASD Level 1 (750 mg/dayx5D) +EIASD Level 2 (1100 mg/dayx5D) +EIASD Level 3 (1700 mg/dayx5D) +EIASD Level 4 (2200 mg/dayx5D) -EIASD Level 1 (750 mg/dayx5D) -EIASD Level 2 (1100 mg/dayx5D) -EIASD Level 3 (1700 mg/dayx5D) -EIASD Level 4 (2200 mg/dayx5D) Non Stratified (Both +EIASD and -EIASD)
Hide Arm/Group Description

subjects on the +EIASD (Level 1) treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 1= 750mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

subjects on the +EIASD (Level 2) treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 2= 1100mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

subjects on the +EIASD (Level 3) treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 3= 1700mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation; Includes pts at the new formulation TC6 (-PEG)

subjects on the +EIASD (Level 4) treatment arm were taking one of these antiseizure durgs: phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine.

Subjects will take terameprocol for 5 consecutive days each month by IV. Dose level 4= 2220mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hypatic enzynmes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 1 = 750mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hypatic enzynmes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 2 = 1100mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hypatic enzynmes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 3 = 1700mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

Subjects in the -EIASD group were either not being treated with antiseizure drugs or were taking ones that did not significantly induce hypatic enzynmes such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagavine, topiramate, zonisamide and felbamate.

Subjects will take terameprocol for 5 consecutive days each month by IV. Level 4 = 2200mg/day. NO intrasubject dose escalation.

PK data will be collected on day one of cycle one infusion

+PEG Formulation

Subjects in this group were not stratified based on anti-seizure medication..

Subjects will take terameprocol for 5 consecutive days each month by IV. This was for dose 2200mg/day.

New formulation TC6 - NONPEG or -PEG.

All-Cause Mortality
+ EIASD Level 1 (750 mg/dayx5D) +EIASD Level 2 (1100 mg/dayx5D) +EIASD Level 3 (1700 mg/dayx5D) +EIASD Level 4 (2200 mg/dayx5D) -EIASD Level 1 (750 mg/dayx5D) -EIASD Level 2 (1100 mg/dayx5D) -EIASD Level 3 (1700 mg/dayx5D) -EIASD Level 4 (2200 mg/dayx5D) Non Stratified (Both +EIASD and -EIASD)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
+ EIASD Level 1 (750 mg/dayx5D) +EIASD Level 2 (1100 mg/dayx5D) +EIASD Level 3 (1700 mg/dayx5D) +EIASD Level 4 (2200 mg/dayx5D) -EIASD Level 1 (750 mg/dayx5D) -EIASD Level 2 (1100 mg/dayx5D) -EIASD Level 3 (1700 mg/dayx5D) -EIASD Level 4 (2200 mg/dayx5D) Non Stratified (Both +EIASD and -EIASD)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/2 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/6 (0.00%)      2/6 (33.33%)      2/3 (66.67%)    
Gastrointestinal disorders                   
illeus  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
General disorders                   
Constitutional Symptoms -other * 2 [1]  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1
Renal and urinary disorders                   
interstitial nephritis * 2  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Respiratory, thoracic and mediastinal disorders                   
dyspnea  2  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
hypoxia  2  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE 3.0
2
Term from vocabulary, CTCAE (3.0)
[1]
Failure to strived
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
+ EIASD Level 1 (750 mg/dayx5D) +EIASD Level 2 (1100 mg/dayx5D) +EIASD Level 3 (1700 mg/dayx5D) +EIASD Level 4 (2200 mg/dayx5D) -EIASD Level 1 (750 mg/dayx5D) -EIASD Level 2 (1100 mg/dayx5D) -EIASD Level 3 (1700 mg/dayx5D) -EIASD Level 4 (2200 mg/dayx5D) Non Stratified (Both +EIASD and -EIASD)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      4/4 (100.00%)      5/5 (100.00%)      1/2 (50.00%)      2/3 (66.67%)      3/3 (100.00%)      6/6 (100.00%)      3/6 (50.00%)      3/3 (100.00%)    
Blood and lymphatic system disorders                   
anemia  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
Cardiac disorders                   
hypertension * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders                   
nausea  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 0/2 (0.00%)  0 2/2 (100.00%)  2 1/3 (33.33%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 1/3 (33.33%)  1
Constipation * 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/3 (33.33%)  1
diarrhea * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
abdominal distension * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
dyspepsia * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  2 1/6 (16.67%)  1 0/3 (0.00%)  0
ileus * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
fecal incontinence * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
dehydration * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
anorexia * 1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/5 (20.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
General disorders                   
fatigue  1  1/3 (33.33%)  1 1/4 (25.00%)  5 1/5 (20.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 3/3 (100.00%)  4 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
injection site reaction NOS  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 1/2 (50.00%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/3 (0.00%)  0
fever * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
General disorders and administration site condistions -other * 1 [1]  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
gait disturbance * 1 [2]  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
Investigations                   
lipase  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
Aspartate aminotransferase increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Alanine aminotransferase increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
platelet count decreased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Metabolism and nutrition disorders                   
hypophosphatemia  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
hypoalbuminemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders                   
back pain * 1 [3]  0/3 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
generalized muscle weakness * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/3 (33.33%)  1
Nervous system disorders                   
Seizure  1  0/3 (0.00%)  0 1/4 (25.00%)  1 1/5 (20.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
dizziness  1  1/3 (33.33%)  2 0/4 (0.00%)  0 1/5 (20.00%)  2 0/2 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
headache * 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
ataxia * 1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
tremor * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 0/3 (0.00%)  0
somnolence * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Psychiatric disorders                   
mood alteration - euphoria * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Renal and urinary disorders                   
proteinuria  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
urinary incontinence * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0
acute kidney injury  1 [4]  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
Respiratory, thoracic and mediastinal disorders                   
hypoxia * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/3 (66.67%)  2
laryngeal inflammation  1 [5]  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1
dyspnea * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders                   
erythrodema  1 [6]  0/3 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0
rash acneiform * 1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/5 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0 2/3 (66.67%)  3
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
failure to thrive
[2]
gait abnormal walking
[3]
Right flank pain
[4]
interstitial nephritis
[5]
pain-larynx
[6]
localised exfoliation
We were not able to complete the phase 2 portion of this study as the company had internal issues and no longer had funds to support the project. We did complete the phase I and determined the (Maxium Tolerated Dose) MTD, 1700mg/day x 5 days
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Director of Adult Brain Tumor Consortum
Organization: Adult Brain Tumor Consortium Central Office - Johns Hopkins
Phone: 410-955-3657
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00404248     History of Changes
Other Study ID Numbers: NABTT-0503 CDR0000515952
U01CA062475 ( U.S. NIH Grant/Contract )
NABTT-0503
First Submitted: November 27, 2006
First Posted: November 28, 2006
Results First Submitted: November 5, 2014
Results First Posted: August 11, 2015
Last Update Posted: March 6, 2019