Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors
| Registry | NCT00020150 |
|---|---|
| Status | Completed |
| Phase | Phase 1 |
| Study type | Interventional; treatment |
| Sponsor | National Cancer Institute (NCI) (Nih) |
| 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 |
| Interventions | O6-benzylguanine, temozolomide (Drug) |
| Dates | start 2000-06-01, first posted 2003-01-27, last updated 2015-04-29 |
| Locations | 1 site in United States |
Related Papers Related Patents Related Grants Related Experts
All trials for Brain and Central Nervous System Tumors All trials for Childhood Germ Cell Tumor All trials of O6-benzylguanine All trials of temozolomide
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.
OBJECTIVES:
* Determine the maximum tolerated dose of temozolomide administered with a biologically active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.
* Determine the dose-limiting toxicity and the toxicity profile of this combination in these patients.
* Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
* Assess the plasma pharmacokinetics of this combination in these patients.
* Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear cells with the degree of hematologic toxicity of this combination in these patients.
OUTLINE: This is a dose-escalation study.
Patients 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.
Sequential 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.
Quality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.
PROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2 years.
Sex: All, ages: any to 21 Years
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
| Facility | City | Country | Status |
|---|---|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland | United States |