Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020150
• Other study ID #: CDR0000067880
• Secondary ID: NCI-00-C-0105INC
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: April 28, 2015
• Start date: June 2000

Study information

• Verified date: August 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Other known NCT identifiers

• NCT00005019

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Kidney Cancer
• Liver Cancer
• Liver Neoplasms
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Neuroblastoma
• Ovarian Cancer
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• O6-benzylguanine

• temozolomide

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & 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: 1 — View 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. — View Citation