Ignite Creation Date:
2025-12-24 @ 5:03 PM
Ignite Modification Date:
2026-01-01 @ 10:09 AM
Study NCT ID:
NCT00020150
Status:
COMPLETED
Last Update Posted:
2015-04-29
First Post:
2001-07-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016543', 'term': 'Central Nervous System Neoplasms'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D008113', 'term': 'Liver Neoplasms'}, {'id': 'D009447', 'term': 'Neuroblastoma'}, {'id': 'D010051', 'term': 'Ovarian Neoplasms'}, {'id': 'D012509', 'term': 'Sarcoma'}, {'id': 'D009396', 'term': 'Wilms Tumor'}, {'id': 'D012516', 'term': 'Osteosarcoma'}, {'id': 'D009837', 'term': 'Oligodendroglioma'}, {'id': 'D016545', 'term': 'Choroid Plexus Neoplasms'}, {'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D008527', 'term': 'Medulloblastoma'}, {'id': 'D020339', 'term': 'Optic Nerve Glioma'}, {'id': 'D018241', 'term': 'Neuroectodermal Tumors, Primitive, Peripheral'}, {'id': 'C531673', 'term': 'Familial ependymoma'}, {'id': 'D013724', 'term': 'Teratoma'}, {'id': 'D013736', 'term': 'Testicular Neoplasms'}, {'id': 'C562841', 'term': 'Ovarian Germ Cell Cancer'}], 'ancestors': [{'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D018242', 'term': 'Neuroectodermal Tumors, Primitive'}, {'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': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D005833', 'term': 'Genital Neoplasms, Female'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D018204', 'term': 'Neoplasms, Connective and Soft Tissue'}, {'id': 'D018193', 'term': 'Neoplasms, Complex and Mixed'}, {'id': 'D009386', 'term': 'Neoplastic Syndromes, Hereditary'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D018213', 'term': 'Neoplasms, Bone Tissue'}, {'id': 'D009372', 'term': 'Neoplasms, Connective Tissue'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D002551', 'term': 'Cerebral Ventricle Neoplasms'}, {'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D019574', 'term': 'Optic Nerve Neoplasms'}, {'id': 'D003390', 'term': 'Cranial Nerve Neoplasms'}, {'id': 'D010524', 'term': 'Peripheral Nervous System Neoplasms'}, {'id': 'D003389', 'term': 'Cranial Nerve Diseases'}, {'id': 'D009901', 'term': 'Optic Nerve Diseases'}, {'id': 'D005128', 'term': 'Eye Diseases'}, {'id': 'D005834', 'term': 'Genital Neoplasms, Male'}, {'id': 'D005832', 'term': 'Genital Diseases, Male'}, {'id': 'D013733', 'term': 'Testicular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C064976', 'term': 'O(6)-benzylguanine'}, {'id': 'D000077204', 'term': 'Temozolomide'}], 'ancestors': [{'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'primaryPurpose': 'TREATMENT'}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2000-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2004-08', 'lastUpdateSubmitDate': '2015-04-28', 'studyFirstSubmitDate': '2001-07-11', 'studyFirstSubmitQcDate': '2003-01-26', 'lastUpdatePostDateStruct': {'date': '2015-04-29', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2003-01-27', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['recurrent childhood rhabdomyosarcoma', 'childhood craniopharyngioma', 'recurrent childhood brain tumor', 'recurrent neuroblastoma', 'recurrent childhood liver cancer', 'recurrent Wilms tumor and other childhood kidney tumors', 'childhood central nervous system germ cell tumor', 'recurrent osteosarcoma', 'unspecified childhood solid tumor, protocol specific', 'childhood germ cell tumor', 'recurrent childhood soft tissue sarcoma', 'childhood oligodendroglioma', 'childhood choroid plexus tumor', 'childhood grade I meningioma', 'childhood grade II meningioma', 'childhood grade III meningioma', 'recurrent childhood cerebellar astrocytoma', 'recurrent childhood cerebral astrocytoma', 'recurrent childhood medulloblastoma', 'recurrent childhood visual pathway and hypothalamic glioma', 'previously treated childhood rhabdomyosarcoma', 'recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor', 'recurrent childhood ependymoma', 'childhood teratoma', 'childhood malignant testicular germ cell tumor', 'childhood extragonadal germ cell tumor', 'childhood malignant ovarian germ cell tumor', 'recurrent childhood malignant germ cell tumor'], 'conditions': ['Brain and Central Nervous System Tumors', 'Childhood Germ Cell Tumor', 'Extragonadal Germ Cell Tumor', 'Kidney Cancer', 'Liver Cancer', 'Neuroblastoma', 'Ovarian Cancer', 'Sarcoma', 'Unspecified Childhood Solid Tumor, Protocol Specific']}, 'referencesModule': {'references': [{'pmid': '19430790', 'type': 'RESULT', 'citation': 'Meany HJ, Warren KE, Fox E, Cole DE, Aikin AA, Balis FM. Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors. Cancer Chemother Pharmacol. 2009 Dec;65(1):137-42. doi: 10.1007/s00280-009-1015-8. Epub 2009 May 9.'}, {'pmid': '16234526', 'type': 'RESULT', 'citation': 'Warren KE, Aikin AA, Libucha M, Widemann BC, Fox E, Packer RJ, Balis FM. Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors. J Clin Oncol. 2005 Oct 20;23(30):7646-53. doi: 10.1200/JCO.2005.02.0024.'}]}, 'descriptionModule': {'briefSummary': 'RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.\n\nPURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating children who have solid tumors that have not responded to previous therapy.', 'detailedDescription': 'OBJECTIVES:\n\n* Determine the maximum tolerated dose of temozolomide administered with a biologically active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.\n* Determine the dose-limiting toxicity and the toxicity profile of this combination in these patients.\n* Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.\n* Assess the plasma pharmacokinetics of this combination in these patients.\n* Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear cells with the degree of hematologic toxicity of this combination in these patients.\n\nOUTLINE: This is a dose-escalation study.\n\nPatients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.\n\nSequential dose escalation of O6-BG is followed by sequential dose escalation of temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.\n\nQuality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.\n\nPROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2 years.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "DISEASE CHARACTERISTICS:\n\n* Histologically confirmed solid tumor refractory to standard therapy and for which no potentially curative therapy exists, including, but not limited to:\n\n * Rhabdomyosarcoma and other soft tissue sarcomas\n * Ewing's family of tumors\n * Osteosarcoma\n * Neuroblastoma\n * Wilms' tumor\n * Hepatic tumors\n * Germ cell tumors\n * Primary brain tumor\n* Histological confirmation may be waived for brainstem or optic gliomas\n* Measurable or evaluable disease\n* Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent disease after prior surgery\n\nPATIENT CHARACTERISTICS:\n\nAge:\n\n* 21 and under\n\nPerformance status:\n\n* ECOG 0-2\n\nLife expectancy:\n\n* At least 8 weeks\n\nHematopoietic:\n\n* Absolute granulocyte count greater than 1,500/mm\\^3\n* Hemoglobin greater than 8 g/dL\n* Platelet count greater than 100,000/mm\\^3\n\nHepatic:\n\n* Bilirubin normal\n* SGPT less than 2 times upper limit of normal\n* No significant hepatic dysfunction\n\nRenal:\n\n* Creatinine normal OR\n* Creatinine clearance at least 60 mL/min\n\nCardiovascular:\n\n* No significant cardiac dysfunction\n\nPulmonary:\n\n* No significant pulmonary dysfunction\n\nOther:\n\n* Not pregnant or nursing\n* Negative pregnancy test\n* Fertile patients must use effective contraception\n* Able to swallow capsules\n* No significant unrelated systemic illness that would preclude study (e.g., serious infections or organ dysfunction)\n* No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol\n\nPRIOR CONCURRENT THERAPY:\n\nBiologic therapy:\n\n* At least 1 week since prior colony-stimulating factors (e.g., filgrastim \\[G- CSF\\], sargramostim \\[GM-CSF\\], or epoetin alfa)\n* At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell transplantation\n* No concurrent anticancer immunotherapy\n\nChemotherapy:\n\n* See Disease Characteristics\n* At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered\n* Prior temozolomide allowed provided not administered within past 3 months, no severe toxicities experienced during prior course, and not given in combination with other agents designed to inactivate alanine-glyoxylate aminotransferase\n* No other concurrent investigational or standard anticancer chemotherapy\n\nEndocrine therapy:\n\n* Concurrent corticosteroids for control of brain tumor-associated edema allowed provided on stable or decreasing dose for at least 1 week prior to study\n\nRadiotherapy:\n\n* See Disease Characteristics\n* At least 4 weeks since prior limited-field radiotherapy\n* At least 4 months since prior craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis\n* Recovered from prior radiotherapy\n* No concurrent anticancer radiotherapy\n\nSurgery:\n\n* See Disease Characteristics\n\nOther:\n\n* At least 4 weeks since other prior investigational therapy and recovered\n* No other concurrent anticancer investigational agents"}, 'identificationModule': {'nctId': 'NCT00020150', 'briefTitle': 'Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors', 'nctIdAliases': ['NCT00005019'], 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors', 'orgStudyIdInfo': {'id': 'CDR0000067880'}, 'secondaryIdInfos': [{'id': 'NCI-00-C-0105I'}, {'id': 'NCI-237'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'O6-benzylguanine', 'type': 'DRUG'}, {'name': 'temozolomide', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892-1182', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'overallOfficials': [{'name': 'Katherine Warren, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'National Cancer Institute (NCI)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}}}}