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High Grade Glioma (III or IV)Phase 1NCT02575794

Terameprocol in Treating Patients With Recurrent High Grade Glioma

A Phase 1 study testing Terameprocol and Pharmacological Study in people with High Grade Glioma (III or IV), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High Grade Glioma (III or IV)
What is being tested?
Terameprocol and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
9 sitesUnited States
Study dates
3 May 2018to 4 Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 12 weeks from the completion of radiation
  • 6 weeks from a nitrosourea chemotherapy
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  • 3 weeks from a non-nitrosourea chemotherapy
  • 4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents
  • 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
  • 4 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
  • Total bilirubin =< institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
  • Patients must be able to provide written informed consent
  • Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
  • Patients must be able to swallow oral medications
  • Part 2 (surgical) patients only: patients must be undergoing surgery that is clinically indicated as determined by their care providers; patients must be eligible for surgical resection according to the following criteria:
  • Expectation that the surgeon is able to resect at least 100 mg of tumor from enhancing tumor and at least 100 mg from non-enhancing tumor with low risk of inducing neurological injury

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294-3410

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Josephine Ford Cancer Center at Henry Ford Hospital

    Detroit, Michigan, 48202

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • Abrams Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Hillman Cancer Center at University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Phase 1 Dose Escalation and Drug Distribution Study of Oral Terameprocol in Patients With Recurrent High Grade Glioma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) of terameprocol given orally on days 1-5 every 28 days in patients with high grade glioma. (Part 1)

II. To evaluate terameprocol tumor to plasma ratios in resected high grade gliomas following 5 days of oral terameprocol administration. (Part 2)

III. To assess the maximum duration of terameprocol that can be safely administered on a continuous basis. (Part 3)

SECONDARY OBJECTIVES:

  1. Characterize the plasma pharmacokinetic (PK) of oral terameprocol.

II. Evaluate the toxicities of oral terameprocol.

III. Assess progression-free survival.

IV. Estimate overall survival.

  1. Assess tumor response.

TERTIARY OBJECTIVES:

  1. Assess the contribution of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) genotypes on the variability of oral terameprocol pharmacokinetics.

OUTLINE: This is a dose-escalation study.

Patients receive terameprocol orally (PO) once daily (QD) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.

Being tested
Terameprocol, Pharmacological Study
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TerameprocolDrug

    Also called 1,1'-(2,3-Dimethyl-1,4-butanediyl)bis(3,4-dimethoxybenzene), EM-1421, M4N, tetra-O-methyl NDGA

    Given PO

  • Pharmacological StudyOther

    Also called Pharnacological Study

    Correlative studies

Study groups in NCT02575794
Study groupRoleWhat they receive
Treatment (terameprocol)ExperimentalPatients receive terameprocol PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Pharmacological Study
Receives: Drug: Terameprocol; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 - Day28 (First Cycle)

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

    The tumor/plasma concentration ratio will be estimated.

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

  3. 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.

    Measured: Up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2015 (estimated)
  2. Study start3 May 2018
  3. Primary completion30 Sep 2023
  4. Study completion4 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02575794
Sponsor's protocol ID
ABTC-1401
Other IDs
IRB00065527, UM1CA137443
Status last verified
Oct 2023
First submitted
9 Oct 2015
Last updated
6 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38955178

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Terameprocol and Pharmacological Study in people with High Grade Glioma (III or IV), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of terameprocol (Part 1) (time frame: Day 1 - Day28 (First Cycle)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02575794, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.

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