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| ID | Type | Description | Link |
|---|---|---|---|
| U01CA062475 | U.S. NIH Grant/Contract | View source | |
| NABTT-0503 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as tetra-O-methyl nordihydroguaiaretic acid (EM-1421), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of EM-1421 and to see how well it works in treating patients with recurrent high-grade glioma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II, open-label study. Patients are stratified according to the use of cytochrome P450-inducing anticonvulsants (use of anticonvulsant drugs that induce hepatic metabolic enzymes vs use of anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes or no use of anticonvulsant drugs).
Cohorts of 3-6 patients receive escalating doses of EM-1421 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
After completion of study therapy, patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| With Enzyme-inducing antiseizure drugs (+EIASD) | Active Comparator | 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 |
|
| With Non enzyme-inducing antiseizure drugs (-EIASD) | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| terameprocol | Drug | terameprocol will be given IV 5 consecutive days every 28 days. Starting dose 750mg/day. Cohorts of 3pts. A Dose Limiting Toxicity (DLT) target rate of Less than or equal to 33%. Dose levels: 750, 1100, 1700, 2200, 3000, 4000, 5300, 7000, 9300 mg. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (Phase I) | 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 | first 30 days of treatment |
| Maximum Tolerated Dose (Phase I) - Dose Limiting Toxicity (DLT) | 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 | First 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - Total Body Clearance | 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. | 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. |
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DISEASE CHARACTERISTICS:
Histologically confirmed malignant glioma, including any of the following subtypes:
Progressive or recurrent disease after radiation therapy with or without chemotherapy
Contrast-enhancing measurable disease by MRI or CT scan
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from prior therapy
At least 3 months since prior radiation therapy
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
At least 2 weeks since prior Federal Drug Administration (FDA)-approved noncytotoxic therapy (e.g., celecoxib or thalidomide)
At least 3 weeks since prior investigational noncytotoxic agents
At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes, including any of the following:
No other concurrent therapy for this tumor, including systemic chemotherapy or radiation therapy
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| Name | Affiliation | Role |
|---|---|---|
| Stuart A. Grossman, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB Comprehensive Cancer Center | Birmingham | Alabama | 35294-3410 | United States | ||
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22323663 | Result | Grossman SA, Ye X, Peereboom D, Rosenfeld MR, Mikkelsen T, Supko JG, Desideri S; Adult Brain Tumor Consortium. Phase I study of terameprocol in patients with recurrent high-grade glioma. Neuro Oncol. 2012 Apr;14(4):511-7. doi: 10.1093/neuonc/nor230. Epub 2012 Feb 8. |
| Label | URL |
|---|---|
| Clinical trial summary from the National Cancer Institute's PDQ® database | View source |
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subjects were accrued 2007-2008 in outpatient clinic
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 Enzyme Inducing Antiseizure Drug (+ EIASD) Level 1 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| pharmacological study | Other | All pts on both arms will have pks, blood collections. 5ml of blood will be drawn on Cycle 1 day 1, Cycle 1 Day 5, Cycle 2 day 1 and Cycle 2 day 5. A total of 10 samples will be drawn at each of these time points. 1hr pre-infusion, 15 min, 1hr, 1.15, 1.5, 2, 3,4,6 and 24hr post infusion. |
|
|
| Pharmacokinetics - Steady-State Apparent Volume Distribution | 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. | 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. |
| Pharmacokinetics - Terminal Phase Half-life | effect of hepatic enzyme-inducing drugs on PKs | 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. |
| Efficacy - Best Overall Response | 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. | About 2 years |
| Survival | Survival measured from first day of treatment to date of death | time to death - up to 12 months |
| Tampa |
| Florida |
| 33612-9497 |
| United States |
| Winship Cancer Institute of Emory University | Atlanta | Georgia | 30322 | United States |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem | North Carolina | 27157-1096 | United States |
| Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | 44195 | United States |
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104-4283 | United States |
| FG001 | Arm 2 +EIASD Level 2 | 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. |
| FG002 | Arm 3 +EIASD Level 3 | 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 |
| FG003 | Arm 4 +EIASD Level 4 | 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. |
| FG004 | Arm 5 Non-Enzyme Inducing Antiseizure Drug (-EIASD) Level 1 | 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 |
| FG005 | Arm 6 -EIASD Level 2 | 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 |
| FG006 | Arm 7 -EIASD Level 3 | 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 |
| FG007 | Arm 8 -EIASD Level 4 | 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 |
| FG008 | Arm 9 - Non Stratified (Both +EIASD and -EIASD) | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
high grade gliomas (GBM, AA or AO) histologically confirmed
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 +EIASD | 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 |
| BG001 | Arm 2 -EIASD | 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 |
| BG002 | Arm 3 no Stratification (+EIASD or -EIASD) | 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 |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Karnofsky Performance Status | 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. | Number | participants |
| |||||||||||||||
| Histologic diagnosis | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (Phase I) | 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 | Posted | Number | mg/day x 5 days | first 30 days of treatment |
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| Primary | Maximum Tolerated Dose (Phase I) - Dose Limiting Toxicity (DLT) | 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 | +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 | Posted | Number | Dose Limiting Toxicities (DLT) | First 30 days |
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| Secondary | Pharmacokinetics - Total Body Clearance | 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. | 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 | Posted | Mean | Standard Deviation | Liters/hour | 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. |
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| Secondary | Pharmacokinetics - Steady-State Apparent Volume Distribution | 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. | 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 | Posted | Mean | Standard Deviation | Liters | 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. |
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| Secondary | Pharmacokinetics - Terminal Phase Half-life | effect of hepatic enzyme-inducing drugs on PKs | 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 | Posted | Mean | Standard Deviation | Hour | 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. |
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| Secondary | Efficacy - Best Overall Response | 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. | 3 pt did not have proper scans to be evaluable for analysis | Posted | Number | participants | About 2 years |
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| Secondary | Survival | Survival measured from first day of treatment to date of death | 3 pts still alive at time of analysis | Posted | Median | Standard Deviation | months | time to death - up to 12 months |
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While patients were actively on treatment and for 30 days post treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | + EIASD Level 1 (750 mg/dayx5D) | 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 | 0 | 3 | 3 | 3 | ||
| EG001 | +EIASD Level 2 (1100 mg/dayx5D) | 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 | 0 | 4 | 4 | 4 | ||
| EG002 | +EIASD Level 3 (1700 mg/dayx5D) | 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) | 0 | 5 | 5 | 5 | ||
| EG003 | +EIASD Level 4 (2200 mg/dayx5D) | 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 | 0 | 2 | 1 | 2 | ||
| EG004 | -EIASD Level 1 (750 mg/dayx5D) | 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 | 0 | 3 | 2 | 3 | ||
| EG005 | -EIASD Level 2 (1100 mg/dayx5D) | 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 | 0 | 3 | 3 | 3 | ||
| EG006 | -EIASD Level 3 (1700 mg/dayx5D) | 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 | 0 | 6 | 6 | 6 | ||
| EG007 | -EIASD Level 4 (2200 mg/dayx5D) | 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 | 2 | 6 | 3 | 6 | ||
| EG008 | Non Stratified (Both +EIASD and -EIASD) | 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. | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| illeus | Gastrointestinal disorders | CTCAE 3.0 | Systematic Assessment |
| |
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| interstitial nephritis | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Constitutional Symptoms -other | General disorders | CTCAE (3.0) | Non-systematic Assessment | Failure to strived |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| injection site reaction NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| erythrodema | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment | localised exfoliation |
|
| nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| headache | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| ataxia | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| lipase | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment | Right flank pain |
|
| proteinuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| abdominal distension | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hypertension | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| ileus | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| fecal incontinence | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| urinary incontinence | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
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| platelet count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
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| rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
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| tremor | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| somnolence | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| fever | General disorders | CTCAE (3.0) | Non-systematic Assessment |
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| General disorders and administration site condistions -other | General disorders | CTCAE (3.0) | Non-systematic Assessment | failure to thrive |
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| acute kidney injury | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | interstitial nephritis |
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| laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment | pain-larynx |
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| dehydration | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| gait disturbance | General disorders | CTCAE (3.0) | Non-systematic Assessment | gait abnormal walking |
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| anorexia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| mood alteration - euphoria | Psychiatric disorders | CTCAE (3.0) | Non-systematic Assessment |
|
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
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Adult Brain Tumor Consortum | Adult Brain Tumor Consortium Central Office - Johns Hopkins | 410-955-3657 | jfisher@jhmi.edu |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D001254 | Astrocytoma |
| D009837 | Oligodendroglioma |
| D005909 | Glioblastoma |
| D001932 | Brain Neoplasms |
| D018316 | Gliosarcoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C076852 | terameprocol |
Not provided
Not provided
Not provided
| Male |
|
| 90 |
|
| 80 |
|
| 70 |
|
| 60 |
|
| anaplastic oligodendroglioma |
|
| anaplastic astrocytoma |
|
| OG002 | +EIASD Level 3 (1700 mg/dayx5D) | 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) |
| OG003 | +EIASD Level 4 (2200 mg/dayx5D) | 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 |
| OG004 | -EIASD Level 1 (750 mg/dayx5D) | 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 |
| OG005 | -EIASD Level 2 (1100 mg/dayx5D) | 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 |
| OG006 | -EIASD Level 3 (1700 mg/dayx5D) | 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 |
| OG007 | -EIASD Level 4 (2200 mg/dayx5D) | 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 |
| OG008 | Non Stratified (Both +EIASD and -EIASD) | 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 ) |
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