Low-dose Temozolomide for 2 Weeks on Brain Tumor Enzyme in Patients With Gliomas (P04602 AM1) (Completed)

This study has been completed.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
First received: January 18, 2007
Last updated: June 11, 2015
Last verified: June 2015
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.

Condition Intervention Phase
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    An experimental assay was developed to measure MGMT levels.

Secondary Outcome Measures:
  • Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

    Grade 3 was defined as severe per Common Terminology Criteria for Adverse Events (CTCAE).

    Grade 4 was defined as life-threatening per CTCAE.

  • Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    An AE was defined as any event which was adverse, including what were commonly described as adverse or undesirable experiences, adverse events, adverse reactions, side effects, or death due to any cause associated with, or observed in conjunction with the use of a drug, biological product, or device in humans, whether or not considered related to the use of that product. Additionally, any event which was associated with, or observed in conjunction with product overdose whether accidental or intentional, or product abuse and/or withdrawal was also considered an AE.

  • Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay.

  • MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay.

Enrollment: 40
Study Start Date: September 2006
Study Completion Date: February 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temozolomide treatment Drug: temozolomide

Temozolomide 75 mg/m^2 daily for 14 days prior to surgery.

As standard of care, it could also be given at the same dose for up to 28 days after surgery, per investigator discretion.

Other Name: SCH 052365
No Intervention: No treatment


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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;
    • Alkaline phosphatase of > 2.5 ULN.
  • Known Human Immunodeficiency Virus [HIV] infection.
  • Known chronic hepatitis B or hepatitis C infection.
  • Any other serious medical condition according to the medical judgment of the physician prior to inclusion in the study.
  • Any medical condition, which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction).
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  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00424554     History of Changes
Other Study ID Numbers: P04602 
Study First Received: January 18, 2007
Results First Received: June 3, 2011
Last Updated: June 11, 2015
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 03, 2016