A Phase II Trial to Evaluate the Effect of Low Dose Temozolomide (TMZ) for 2 Weeks on Brain Tumor O-6-methylguanine-DNA Methyltransferase (MGMT) Activity in Patients With Gliomas.

Merck Sharp & Dohme LLC0 sites40 target enrollmentSeptember 26, 2006

ConditionsGlioma

Interventionstemozolomide

Drugstemozolomide

Overview

Phase: Phase 2
Intervention: temozolomide
Conditions: Glioma
Sponsor: Merck Sharp & Dohme LLC
Enrollment: 40
Primary Endpoint: MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The main purpose of this study is to assess the effect of a two-week pre-surgery treatment with low-dose temozolomide (TMZ) on brain tumor methylguanine-DNA (deoxyribonucleic acid) methyltransferase (MGMT) activity in patients with gliomas.

Registry

clinicaltrials.gov

Start Date

September 26, 2006

End Date

February 16, 2011

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Presence of a brain tumor with high probability of being a glioma as detected by Magnetic Resonance Imaging (MRI). These would include newly diagnosed tumors or potentially recurrent gliomas.
•No prior treatment for the tumor including chemotherapy or radiotherapy.
•Amenable to surgery for biopsy or resection of the brain tumor. Surgically confirmed diagnosis of glioma (glioblastoma multiforme \[GBM\], anaplastic astrocytoma \[AA\], anaplastic oligodendroglioma \[AO\], anaplastic oligoastrocytoma \[AOA\], astrocytoma \[A\] or oligodendroglioma \[O\]) will be
•required for patients to be maintained in the study. Those not fulfilling this requirement will be discontinued and will be replaced.
•Use of medically approved contraception in fertile males and females.
•Women with childbearing potential must have a negative urine or serum
•pregnancy test (urinary excretion or serum level of beta-Human Chorionic
•Gonadotropin \[bHCG\]) within 72 hours of randomization.
•Karnofsky Performance Status score \>= 70%.
•Signed informed consent form

Exclusion Criteria

•Prior chemotherapy.
•Prior radiotherapy at the tumor site.
•History of non-compliance to other therapies.
•Inadequate haematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days, inclusive, prior to study inclusion):
•Absolute neutrophil count ≤1.5 x 10\^9/L;
•Platelets ≤100 x 10\^9/L;
•Haemoglobin \<90 g/L;
•Serum creatinine ≥1.5 times upper limit of laboratory normal;
•Total serum bilirubin ≥1.5 times upper limit of laboratory normal (ULN);
•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.0 ULN;

Arms & Interventions

Temozolomide treatment

Intervention: temozolomide

Outcomes

Primary Outcomes

MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery

Time Frame: 14 days

An experimental assay was developed to measure MGMT levels.

Secondary Outcomes

MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels(14 days)
Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities(12 months)
Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE)(12 months)
Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor(14 days)