Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

NCT00020150 | Completed Phase 1

• 3 other identifiers: CDR0000067880NCI-00-C-0105INCI-237
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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. PURPOSE: 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.

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

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

Interventions

O6-benzylguanine DRUG

temozolomide DRUG

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed solid tumor refractory to standard therapy and for which no potentially curative therapy exists, including, but not limited to: * Rhabdomyosarcoma and other soft tissue sarcomas * Ewing's family of tumors * Osteosarcoma * Neuroblastoma * Wilms' tumor * Hepatic tumors * Germ cell tumors * Primary brain tumor * Histological confirmation may be waived for brainstem or optic gliomas * Measurable or evaluable disease * Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent disease after prior surgery PATIENT CHARACTERISTICS: Age: * 21 and under Performance status: * ECOG 0-2 Life expectancy: * At least 8 weeks Hematopoietic: * Absolute granulocyte count greater than 1,500/mm\^3 * Hemoglobin greater than 8 g/dL * Platelet count greater than 100,000/mm\^3 Hepatic: * Bilirubin normal * SGPT less than 2 times upper limit of normal * No significant hepatic dysfunction Renal: * Creatinine normal OR * Creatinine clearance at least 60 mL/min Cardiovascular: * No significant cardiac dysfunction Pulmonary: * No significant pulmonary dysfunction Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow capsules * No significant unrelated systemic illness that would preclude study (e.g., serious infections or organ dysfunction) * No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 1 week since prior colony-stimulating factors (e.g., filgrastim \[G- CSF\], sargramostim \[GM-CSF\], or epoetin alfa) * At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell transplantation * No concurrent anticancer immunotherapy Chemotherapy: * See Disease Characteristics * At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered * 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 * No other concurrent investigational or standard anticancer chemotherapy Endocrine therapy: * Concurrent corticosteroids for control of brain tumor-associated edema allowed provided on stable or decreasing dose for at least 1 week prior to study Radiotherapy: * See Disease Characteristics * At least 4 weeks since prior limited-field radiotherapy * At least 4 months since prior craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis * Recovered from prior radiotherapy * No concurrent anticancer radiotherapy Surgery: * See Disease Characteristics Other: * At least 4 weeks since other prior investigational therapy and recovered * No other concurrent anticancer investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, 20892-1182, United States

Location

Related Publications (2)

• 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: 19430790 RESULT

• 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.

  PMID: 16234526 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Kidney Neoplasms; Liver Neoplasms; Neuroblastoma; Ovarian Neoplasms; Sarcoma; Wilms Tumor; Osteosarcoma; Oligodendroglioma; Choroid Plexus Neoplasms; Astrocytoma; Medulloblastoma; Optic Nerve Glioma; Neuroectodermal Tumors, Primitive, Peripheral; Familial ependymoma; Teratoma; Testicular Neoplasms; Ovarian Germ Cell Cancer

Interventions

O(6)-benzylguanine; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Glioma; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Testicular Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Katherine Warren, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 11, 2001
• First Posted: January 27, 2003
• Study Start: June 1, 2000
• Last Updated: April 29, 2015

Record last verified: 2004-08

Locations

US (1)