Temozolomide Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme (Study P04661)(COMPLETED)

Study Overview
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Brief Summary
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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.

Official Title
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SCH 52365 Phase II Clinical Study in Patients With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Glioblastoma

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>It is the only arm of the study. Subjects receive a combination of radiotherapy and temozolomide, and then temozolomide monotherapy. | Radiation: Radiotherapy<br>* 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.<br>* Other names: Irradiation, radiation therapy;Drug: Temozolomide<br>* 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.<br>* Other names: Temodal, Temodar, SCH 052365;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events With an Incidence of Greater Than or Equal to 20% | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. Adverse events were classified under the system organ class using MedDRA-J Version 11.0. | until 30 days after the completion of administration of monotherapy | 
| Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. | until 30 days after the completion of administration of monotherapy | 
| Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. | until 30 days after the completion of administration of monotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progression Free Survival (PFS) for 1 Year | Administration of SCH 52365 was continued until progression was observed (progression was judged by the investigator based on MRI and clinical symptoms). | 1 year after the start of admininstration in the concomitant radiotherapy phase | 
| Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response | CR = measurable lesion disappeared. PR = total sum of lesions measurable in bidimension decreased by 50% or more on whole and no secondary progression attributable to tumor was noted. No onset of new lesion. | 1 year after the start of administration in the concomitant radiotherapy phase |