Terameprocol in Treating Patients With Recurrent High Grade Glioma

NCT02575794 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: ABTC-1401IRB00065527UM1CA137443
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 9

Brief Summary

This phase I trial studies the side effects and best dose of terameprocol in treating patients with high-grade glioma that has come back. Drugs used in chemotherapy, such as terameprocol, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

High Grade Glioma (III or IV)

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose of terameprocol (Part 1)

  To estimate the MTDs in terms of clinical toxicities, a modified continual reassessment method, based on that described by Piantadosi et al. will be employed. Dose escalation will be guided by observed clinical toxicity in 3 patients per dose cohort after the initial dose.

  Day 1 - Day28 (First Cycle)

• Change in terameprocol tumor to plasma concentration ratio (Part 2)

  The tumor/plasma concentration ratio will be estimated.

  Baseline, Pre-surgery (shortly before start of surgery - within 1hr) and post surgery (as soon as practical afer completion of surgery - approx 4 hrs)

• Maximum tolerated days of terameprocol dosing that can safely be administered on a continuous basis (Part 3)

  This is a escalation study. The escalation is the number of continuous days that terameprocol can be given. Terameprocol dose will remain constant at a fix dose everyday.

  Up to 28 days

Study Arms (1)

Treatment (terameprocol)

EXPERIMENTAL

Patients receive terameprocol PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Pharmacological Study

Drug: Terameprocol; Other: Pharmacological Study

Interventions

Terameprocol DRUG

Given PO

Also known as: 1,1'-(2,3-Dimethyl-1,4-butanediyl)bis(3,4-dimethoxybenzene), EM-1421, M4N, tetra-O-methyl NDGA, Tetra-O-methyl Nordihydroguaiaretic Acid, TMNDGA

Treatment (terameprocol)

Pharmacological Study OTHER

Correlative studies

Also known as: Pharnacological Study

Treatment (terameprocol)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed supratentorial high grade glioma (grade III or IV glioma) that is progressive or recurrent following radiation therapy and chemotherapy; patients with grade IV glioma must have progressed or recurred after initial treatment with radiation and temozolomide; patients with grade III glioma must have received at least radiation and one regimen of chemotherapy (temozolomide or procarbazine, lomustine, vincristine \[PCV\] regimen)
• Patients must have measurable contrast-enhancing disease by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to undergo MRI of the brain with gadolinium
• Patients may have had treatment for an unlimited number of prior relapses
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
• weeks from prior antiangiogenesis therapy (approved or investigational) (e.g., bevacizumab, aflibercept, ramucirumab, cediranib, cabozantinib, etc.)
• Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• Patients must be 18 years of age or older
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL

You may not qualify if:

• Patients receiving any other investigational agents are ineligible
• Patient must not have known sensitivity to terameprocol or any formulation excipients
• Patients with (mean of triplicate) QTc(F) \>/= 450mS on screening 12-lead triplicate electrocardiogram (ECG) are ineligible
• Patients must not be on any anticoagulation
• Patients on any moderate or strong cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9) inducer (e.g., carbamazepine, rifampin) or inhibitor (e.g., amiodarone, fluconazole) are ineligible; CYP2C9 poor metabolizers will not be excluded
• Patients on narrow-therapeutic drugs that are substrates for cytochrome P450 family 1, subfamily A, polypeptide 2 (CYP1A2), CYP2C9, cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19), and cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, phenytoin, pimozide, quinidine, sirolimus, tacrolimus, theophylline, tizanidine, warfarin)
• Patient must not have prior gastrointestinal (GI) surgery or GI disease that might interfere with the absorption of terameprocol
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with terameprocol
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Erimos Pharmaceuticals: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (9)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abrams Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Ahluwalia MS, Ozair A, Rudek M, Ye X, Holdhoff M, Lieberman FS, Piotrowski AF, Nabors B, Desai A, Lesser G, Huang RC, Glenn S, Khosla AA, Peereboom DM, Wen PY, Grossman SA. A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR). Cell Rep Med. 2024 Jul 16;5(7):101630. doi: 10.1016/j.xcrm.2024.101630. Epub 2024 Jul 1.

  PMID: 38955178 DERIVED

MeSH Terms

Conditions

Glioma

Interventions

terameprocol

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Manmeet Ahluwalia, MD

  ABTC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 15, 2015
• Study Start: May 3, 2018
• Primary Completion: September 30, 2023
• Study Completion: October 4, 2023
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)