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Terameprocol in Treating Patients With Recurrent High Grade Glioma

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ClinicalTrials.gov Identifier: NCT02575794
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : May 14, 2018
Sponsor:
Collaborator:
Erimos Pharmaceuticals
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
High Grade Glioma (III or IV) Drug: Terameprocol Other: Pharmacological Study Phase 1

Detailed 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.


Study Type : Interventional
Estimated Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Dose Escalation and Drug Distribution Study of Oral Terameprocol in Patients With Recurrent High Grade Glioma
Actual Study Start Date : May 3, 2018
Estimated Primary Completion Date : December 15, 2021
Estimated Study Completion Date : December 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (terameprocol)

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
Given PO
Other Names:
  • 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

Other: Pharmacological Study
Correlative studies
Other Name: Pharnacological Study




Primary Outcome Measures :
  1. Maximum tolerated dose of terameprocol (Part 1) [ Time Frame: Day 1 - Day28 (First Cycle) ]
    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.

  2. Change in terameprocol tumor to plasma concentration ratio (Part 2) [ Time Frame: Baseline, Pre-surgery (shortly before start of surgery - within 1hr) and post surgery (as soon as practical afer completion of surgery - approx 4 hrs) ]
    The tumor/plasma concentration ratio will be estimated.

  3. Maximum tolerated days of terameprocol dosing that can safely be administered on a continuous basis (Part 3) [ Time Frame: Up to 28 days ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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:

      • 12 weeks from the completion of radiation
      • 6 weeks from a nitrosourea chemotherapy
      • 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 have a life expectancy of at least 8 weeks
    • 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 must not have known impaired cardiac function or clinically significant cardiac disease
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02575794


Contacts
Contact: Serena Desideri, MD 410-614-4400 sdeside1@jhmi.edu
Contact: Joy Fisher, MA 410-955-3657 jfisher@jhmi.edu

Locations
United States, Alabama
UAB Comprehensive Cancer Center Not yet recruiting
Birmingham, Alabama, United States, 35294-3410
Contact: Thiru Pillay, RN    205-934-1842    thiru@uab.edu   
Principal Investigator: Burt Nabors, MD         
United States, California
Jonsson Comprehensive Cancer Center at UCLA Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Timothy Cloughesy, MD    310-825-5321    TCloughesy@mednet.ucla.edu   
Principal Investigator: Timothy Cloughesy, MD         
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Quinn qta@jhmi.edu, RN    410-955-8837    qta@jhmi.edu   
Contact: Trisha Surakus    410-502-9864    tsuraku1@jhmi.edu   
Sub-Investigator: Matthias Holdhoff, MD         
Principal Investigator: Stuart Grossman, MD         
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Jennifer Barrs    617-632-6119    JenniferA_Barrs@DFCI.HARVARD.EDU   
Principal Investigator: Patrick Wen, MD         
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Amy Williamson, RN       awillia12@hfhs.org   
Contact: Emily Krozek, MHSA       Ekrozek1@hfhs.org   
Principal Investigator: Tobias Walbert, MD         
United States, North Carolina
Wake Forest University Comprehensive Cancer Center Not yet recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Clinical Trials Office    336-713-6771      
Principal Investigator: Glenn Lesser, MD         
United States, Ohio
Cleveland Clinic Taussig Cancer Center Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Cancer Center-Cares    216-444-7923      
Sub-Investigator: David Peereboom, MD         
United States, Pennsylvania
Abrams Cancer Center of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Clinical Trials Office-Abrams Cancer Center    800-474-9892      
Principal Investigator: Arati Desai, MD         
Hillman Cancer Center at University of Pittsburgh Cancer Institute Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers    412-647-8073      
Principal Investigator: Frank Lieberman, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Erimos Pharmaceuticals
Investigators
Principal Investigator: Manmeet Ahluwalia, MD ABTC

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02575794     History of Changes
Other Study ID Numbers: ABTC-1401
IRB00065527 ( Other Identifier: JHM IRB )
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Masoprocol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Lipoxygenase Inhibitors
Enzyme Inhibitors
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents