Temozolomide Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme (Study P04661)(COMPLETED)
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: Radiotherapy; Temozolomide
Intervention description: Radiotherapy will be administered in combination with temozolomide during the concomitant radiotherapy phase. Radiotherapy will consist of a conventionally fractioned regimen, delivering a total dose of 60 Gy in 6 weeks, in a once daily schedule of 2 Gy per fraction, for a total of 30 fractions. Radiation will be provided by a linear accelerator of x ray energy of 4 MV or higher.; During the concomitant radiotherapy phase (6 weeks), temozolomide will be administered in combination with radiotherapy, once daily at 75 mg/m2/day. Then, during the monotherapy phase, subjects will receive 6 cycles of temozolomide alone. Each cycle will last 28 days, and temozolomide will be administered once daily from Day 1 to Day 5 of each cycle. The dose of temozolomide in the first cycle will be 150 mg/m2/day, and may be increased to 200 mg/m2/day for Cycle 2 and subsequent cycles depending on nonhematologic toxicity observed and neutrophil and platelet count values. Capsules containing 5 mg, 20 mg, or 100 mg of temozolomide will be combined to achieve each subject's calculated dose.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety of combination therapy of radiotherapy
      and temozolomide ("concomitant radiotherapy phase"), and then temozolomide monotherapy
      ("monotherapy phase"), in patients with newly diagnosed glioblastoma multiforme. Progression
      free survival and response rate will also be calculated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histopathologically confirmed newly diagnosed glioblastoma multiforme with WHO grade
             IV.

          -  Histological diagnosis must be made locally after biopsy or neurosurgical tumor
             resection.

          -  Four or more unstained tissue sections or a paraffin block must be provided to the
             Pathological Judgment Committee as tissue specimens.

          -  Initial surgery/biopsy at diagnosis performed <=6 weeks (42 days) prior to treatment
             with temozolomide.

          -  Age: >=18 and <=70 years.

          -  ECOG performance status <=2.

          -  Stable, non-increasing dose of corticosteroids over the 14 days prior to treatment
             with temozolomide.

          -  No prior chemotherapy or radiotherapy.

          -  Laboratory test values obtained within 14 days before initiation of administration of
             temozolomide must satisfy the following criteria:

               -  absolute neutrophil count >= 1500/mm^3;

               -  platelet count >= 100,000/mm^3;

               -  serum creatinine <=1.5 times the upper limit of laboratory normal;

               -  total bilirubin <=1.5 times the upper limit of laboratory normal;

               -  glutamic oxaloacetic transaminase or glutamic pyruvic transaminase <2.5 times the
                  upper limit of laboratory normal;

               -  alkaline phosphatase < 2.5 times the upper limit of laboratory normal.

          -  Absence of pathological conditions that interfere with taking oral drugs.

          -  Contraception during the study period (from informed consent to the day of the last
             observation/examination of this study) is required in sexually active, potentially
             fertile patients, regardless of sex, under the supervision of the investigator or
             sub-investigator.

          -  The investigator and/or subinvestigator must judge that life expectancy is 12 weeks or
             more.

          -  Patients may be included regardless of sex or inpatient/outpatient.

        Exclusion Criteria:

          -  Extensively disseminated glioblastoma multiforme.

          -  Severe disorders in the heart, liver, kidney, blood, etc.

          -  Presence of previous or concurrent malignancies at other sites with the exception of
             surgically cured carcinoma in-situ of the cervix and non melanoma skin cancer.

          -  Women who are pregnant or lactating.

          -  Women who may be pregnant or who could become pregnant and do not adopt contraception
             method(s).

          -  Participation in another clinical study within 6 weeks prior to the initiation of
             administration of temozolomide.

          -  Subjects who the investigator and/or subinvestigator judged inappropriate to
             participate in the study.