Ignite Creation Date:
2025-12-25 @ 1:45 AM
Ignite Modification Date:
2026-01-08 @ 4:24 PM
Study NCT ID:
NCT02575794
Status:
COMPLETED
Last Update Posted:
2023-10-06
First Post:
2015-10-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Terameprocol in Treating Patients With Recurrent High Grade Glioma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005910', 'term': 'Glioma'}], 'ancestors': [{'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C076852', 'term': 'terameprocol'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-05-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-10', 'completionDateStruct': {'date': '2023-10-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-10-04', 'studyFirstSubmitDate': '2015-10-09', 'studyFirstSubmitQcDate': '2015-10-12', 'lastUpdatePostDateStruct': {'date': '2023-10-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-10-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2023-09-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum tolerated dose of terameprocol (Part 1)', 'timeFrame': 'Day 1 - Day28 (First Cycle)', 'description': '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.'}, {'measure': 'Change in terameprocol tumor to plasma concentration ratio (Part 2)', 'timeFrame': 'Baseline, Pre-surgery (shortly before start of surgery - within 1hr) and post surgery (as soon as practical afer completion of surgery - approx 4 hrs)', 'description': 'The tumor/plasma concentration ratio will be estimated.'}, {'measure': 'Maximum tolerated days of terameprocol dosing that can safely be administered on a continuous basis (Part 3)', 'timeFrame': 'Up to 28 days', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['High Grade Glioma (III or IV)']}, 'referencesModule': {'references': [{'pmid': '38955178', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. 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)\n\nII. To evaluate terameprocol tumor to plasma ratios in resected high grade gliomas following 5 days of oral terameprocol administration. (Part 2)\n\nIII. To assess the maximum duration of terameprocol that can be safely administered on a continuous basis. (Part 3)\n\nSECONDARY OBJECTIVES:\n\nI. Characterize the plasma pharmacokinetic (PK) of oral terameprocol.\n\nII. Evaluate the toxicities of oral terameprocol.\n\nIII. Assess progression-free survival.\n\nIV. Estimate overall survival.\n\nV. Assess tumor response.\n\nTERTIARY OBJECTIVES:\n\nI. Assess the contribution of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) genotypes on the variability of oral terameprocol pharmacokinetics.\n\nOUTLINE: This is a dose-escalation study.\n\nPatients 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.\n\nAfter completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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)\n\n * 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\n * Patients may have had treatment for an unlimited number of prior relapses\n * Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:\n\n * 12 weeks from the completion of radiation\n * 6 weeks from a nitrosourea chemotherapy\n * 3 weeks from a non-nitrosourea chemotherapy\n * 4 weeks from any investigational (not Food and Drug Administration \\[FDA\\]-approved) agents\n * 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)\n * 4 weeks from prior antiangiogenesis therapy (approved or investigational) (e.g., bevacizumab, aflibercept, ramucirumab, cediranib, cabozantinib, etc.)\n * 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)\n * Patients must be 18 years of age or older\n * Absolute neutrophil count \\>= 1,500/mcL\n * Platelets \\>= 100,000/mcL\n * Hemoglobin \\>= 9 g/dL\n * Total bilirubin =\\< institutional upper limit of normal\n * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\< 3 x institutional upper limit of normal\n * Creatinine =\\< institutional upper limit of normal OR creatinine clearance \\>= 60 ml/min/1.73 m\\^2 for patients with creatinine levels above institutional normal\n * Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =\\< 1.5 x institutional upper limit of normal\n * Patients must be able to provide written informed consent\n * 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\n * 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\n * Patients must be able to swallow oral medications\n * 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:\n\n * 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\n\nExclusion Criteria:\n\n* Patients receiving any other investigational agents are ineligible\n* Patient must not have known sensitivity to terameprocol or any formulation excipients\n* Patients with (mean of triplicate) QTc(F) \\>/= 450mS on screening 12-lead triplicate electrocardiogram (ECG) are ineligible\n* Patients must not be on any anticoagulation\n* 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\n* 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)\n* Patient must not have prior gastrointestinal (GI) surgery or GI disease that might interfere with the absorption of terameprocol\n* 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\n* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with terameprocol\n* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy'}, 'identificationModule': {'nctId': 'NCT02575794', 'briefTitle': 'Terameprocol in Treating Patients With Recurrent High Grade Glioma', 'organization': {'class': 'OTHER', 'fullName': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins'}, 'officialTitle': 'Phase 1 Dose Escalation and Drug Distribution Study of Oral Terameprocol in Patients With Recurrent High Grade Glioma', 'orgStudyIdInfo': {'id': 'ABTC-1401'}, 'secondaryIdInfos': [{'id': 'IRB00065527', 'type': 'OTHER', 'domain': 'JHM IRB'}, {'id': 'UM1CA137443', 'link': 'https://reporter.nih.gov/quickSearch/UM1CA137443', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (terameprocol)', 'description': 'Patients receive terameprocol PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\n\nPharmacological Study', 'interventionNames': ['Drug: Terameprocol', 'Other: Pharmacological Study']}], 'interventions': [{'name': 'Terameprocol', 'type': 'DRUG', 'otherNames': ["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'], 'description': 'Given PO', 'armGroupLabels': ['Treatment (terameprocol)']}, {'name': 'Pharmacological Study', 'type': 'OTHER', 'otherNames': ['Pharnacological Study'], 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (terameprocol)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294-3410', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'UAB Comprehensive Cancer Center', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '21231', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Dana Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48202', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Josephine Ford Cancer Center at Henry Ford Hospital', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '10021', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan-Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '27157', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest University Comprehensive Cancer Center', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}, {'zip': '44195', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Cleveland Clinic Taussig Cancer Center', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Abrams Cancer Center of the University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '15232', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Hillman Cancer Center at University of Pittsburgh Cancer Institute', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}], 'overallOfficials': [{'name': 'Manmeet Ahluwalia, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'ABTC'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins', 'class': 'OTHER'}, 'collaborators': [{'name': 'Erimos Pharmaceuticals', 'class': 'INDUSTRY'}, {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}