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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00424554
Recruitment Status : Completed
First Posted : January 19, 2007
Results First Posted : June 29, 2011
Last Update Posted : June 7, 2017
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Glioma Drug: temozolomide Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Actual Study Start Date : September 26, 2006
Actual Primary Completion Date : January 11, 2010
Actual Study Completion Date : February 16, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities [ Time Frame: 12 months ]

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

    Grade 4 was defined as life-threatening per CTCAE.

  2. Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE) [ Time Frame: 12 months ]
    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.

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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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).

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00424554     History of Changes
Other Study ID Numbers: P04602
First Posted: January 19, 2007    Key Record Dates
Results First Posted: June 29, 2011
Last Update Posted: June 7, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents