Terameprocol in Treating Patients With Recurrent High Grade Glioma

  • STATUS
    Recruiting
  • End date
    Dec 15, 2022
  • participants needed
    23
  • sponsor
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Updated on 25 April 2021

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.

Description

PRIMARY OBJECTIVES:

I. 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:

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

II. Evaluate the toxicities of oral terameprocol.

III. Assess progression-free survival.

IV. Estimate overall survival.

V. Assess tumor response.

TERTIARY OBJECTIVES:

I. 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.

Details
Condition High Grade Glioma, malignant glioma
Treatment pharmacological study, Terameprocol
Clinical Study IdentifierNCT02575794
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last Modified on25 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note