NCT00404248

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2007

Longer than P75 for phase_1

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 27, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 28, 2006

Completed
1 month until next milestone

Study Start

First participant enrolled

January 1, 2007

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2012

Completed
3.5 years until next milestone

Results Posted

Study results publicly available

August 11, 2015

Completed
Last Updated

March 6, 2019

Status Verified

March 1, 2019

Enrollment Period

2.4 years

First QC Date

November 27, 2006

Results QC Date

November 5, 2014

Last Update Submit

March 1, 2019

Conditions

Brain and Central Nervous System Tumors

Keywords

adult anaplastic astrocytomaadult anaplastic oligodendrogliomaadult giant cell glioblastomarecurrent adult brain tumoradult glioblastomaadult gliosarcoma

Outcome Measures

Primary Outcomes (2)

  • 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

Secondary Outcomes (5)

  • Pharmacokinetics - Total Body Clearance

    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 - Steady-State Apparent Volume Distribution

    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

    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

    About 2 years

  • Survival

    time to death - up to 12 months

Study Arms (2)

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

Drug: terameprocolOther: pharmacological study

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

Drug: terameprocolOther: pharmacological study

Interventions

terameprocolDRUG

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.

Also known as: EM-1421
With Enzyme-inducing antiseizure drugs (+EIASD)With Non enzyme-inducing antiseizure drugs (-EIASD)
pharmacological studyOTHER

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.

Also known as: PK
With Enzyme-inducing antiseizure drugs (+EIASD)With Non enzyme-inducing antiseizure drugs (-EIASD)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically confirmed malignant glioma, including any of the following subtypes: * Anaplastic astrocytoma * Anaplastic oligodendroglioma * Glioblastoma multiforme * Progressive or recurrent disease after radiation therapy with or without chemotherapy * Patients with a previous low-grade glioma that has progressed to biopsy-confirmed high-grade glioma after radiation therapy with or without chemotherapy are eligible * Contrast-enhancing measurable disease by MRI or CT scan PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Absolute neutrophil count ≥ 1,500/mm³ * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100,000/mm³ * Creatinine ≤ 1.5 mg/dL * Bilirubin ≤ 1.5 mg/dL * Transaminases ≤ 4 times upper limit of normal * Prothrombin Time (PT)/partial thromboplastin time (PTT) /international normalized ratio (INR) normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 2 months after completion of study treatment * Mini Mental State Exam score ≥ 15 * No serious concurrent infection or medical illness that would impair the ability to safely receive study treatment * No other prior or concurrent malignancy within the past 5 years except for curatively treated carcinoma in situ or basal cell carcinoma of the skin * No known sensitivity to any of the study medication components (i.e., polyethylene glycol \[PEG 300\] and 2-hydroxypropyl β-cyclodextrin) 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: * Phenytoin * Carbamazepine * Phenobarbital * Primidone * Oxcarbazepine * Ethosuximide * No other concurrent therapy for this tumor, including systemic chemotherapy or radiation therapy * Concurrent steroids allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (9)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Related Publications (1)

  • 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.

    PMID: 22323663RESULT

Related Links

MeSH Terms

Conditions

Central Nervous System NeoplasmsAstrocytomaOligodendrogliomaGlioblastomaBrain NeoplasmsGliosarcoma

Interventions

terameprocol

Condition Hierarchy (Ancestors)

Nervous System NeoplasmsNeoplasms by SiteNeoplasmsNervous System DiseasesGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueBrain DiseasesCentral Nervous System Diseases

Limitations and Caveats

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

Results Point of Contact

Title
Director of Adult Brain Tumor Consortum
Organization
Adult Brain Tumor Consortium Central Office - Johns Hopkins
jfisher@jhmi.edu
410-955-3657

Study Officials

  • Stuart A. Grossman, MD

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 27, 2006

First Posted

November 28, 2006

Study Start

January 1, 2007

Primary Completion

June 1, 2009

Study Completion

February 1, 2012

Last Updated

March 6, 2019

Results First Posted

August 11, 2015

Record last verified: 2019-03

Locations

US(9)