Standard Temodal (Temozolomide) Regimen Versus Standard Regimen Plus Early Postsurgery Temodal for Newly Diagnosed Glioblastoma Multiforme (Study P05572)

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the efficacy and safety of early postsurgery temozolomide chemotherapy followed by the standard temozolomide regimen, compared to the standard regimen alone, for the treatment of patients with newly diagnosed glioblastoma multiforme.

Official Title
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A Clinical Study of Standard TEMODAL® Regimen Versus Standard Regimen Plus Early Post-Surgery TEMODAL® Chemotherapy in Treatment on Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only the patients who meet all these criteria can be enrolled in the study: Patients with prior histological confirmation of newly diagnosed primary glioblastoma multiforme in supratentorial cerebral hemisphere. Gross total resection or partial resection (imaging) >70%. At least be capable to obtain a tissue sample for MGMT analysis during surgery. Chemo-radiotherapy to be expected from Week 5 (Day 29) after surgery. Age >=18 and <=70 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy >=9 months. Laboratory test values must satisfy the following criteria: absolute neutrophil count >=1.5 x 10^9/L; platelet count >=100 x 10^9/L; hemoglobin >=80 g/L; blood urea nitrogen and creatinine < 1.5 x upper limit of normal value (ULN); total bilirubin and direct bilirubin < 1.5 x ULN; alanine aminotransferase and aspartate aminotransferase < 3 x ULN; alkaline phosphatase < 2 x ULN. Patients must be willing to provide written informed consent. Patients of child-bearing potential (including female subjects and the female partners of male subjects) must use an effective method of contraception. Exclusion Criteria: Patients will not be enrolled if any of the following criteria apply: Patient with previous or current malignancies (except melanoma) at other sites, unless disease free for at least 3 years. Patient who received chemotherapy, radiotherapy for study indication, or other medications for antitumor indication prior to surgery. Patient with recurrent or multiple malignant glioma (including gliomatosis cerebri). Patient with metastatic lesions at the subtentorial or outside of calvaria. Patient who received chemotherapy or radiotherapy sensitizers for head or neck tumor. Patient who received radiotherapy at head or neck which leads to radiotherapy domain overlapping. Patient with acute infections requiring intravenous antibiotics. Frequent vomiting or medical condition that could interfere with oral medication intake (eg, partial bowel obstruction). Known human immunodeficiency virus (HIV)-positive or acquired immune deficiency syndrome (AIDS)-related illness. Woman who is pregnant or breastfeeding. Patient with a history of hypersensitivity to temozolomide or other analogic alkylating agents. Patient with any other conditions under which investigators think the subject is not suitable for enrolment, such like having known that the subject may not have good compliance.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Temozolomide + Radiation<br>Standard therapy regimen: Treatment will start 4 weeks after surgery. Temozolomide will be administered concomitantly with radiotherapy, at 75 mg/m^2/day orally for 42 days. Four weeks after completing concomitant radiotherapy, temozolomide will be administered for an additional six cycles. 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/m^2/day, and may be increased to 200 mg/m^2/day for Cycle 2 and subsequent cycles depending on nonhematological toxicity observed and neutrophil and platelet count values. Capsules containing 20 mg or 100 mg of temozolomide will be used. Radiotherapy will be administered in combination with temozolomide. Radiotherapy will be administered for a total daily dose of 60 Gy in 30 fractions, 5 days a week for 6 weeks. | Drug: Temozolomide<br> <br> * Other names: SCH 052365;Radiation: Radiotherapy<br> <br> * Other names: radiation therapy;|
| Experimental: Temozolomide alone, then Temozolomide + Radiation<br>Early postsurgery temozolomide chemotherapy plus standard regimen: Treatment with temozolomide alone will start 2 weeks after surgery at 75 mg/m^2/day orally for 14 days. Then, starting on Day 29 after surgery, temozolomide will be administered according to standard treatment as described for the temozolomide + radiation arm (standard therapy regimen). Radiotherapy will be administered in combination with temozolomide. Radiotherapy will be administered for a total daily dose of 60 Gy in 30 fractions, 5 days a week for 6 weeks. | Drug: Temozolomide<br> <br> * Other names: SCH 052365;Radiation: Radiotherapy<br> <br> * Other names: radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to death. OS was calculated by the Kaplan-Meier method. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the length of time from randomization to disease progression (the length of time during which the cancer did not get worse) or death. PFS was calculated by the Kaplan-Meier method. | Up to 2 years | 
| Objective Tumor Assessment After Surgery: Overall Response | Overall response was based on neuroimaging (magnetic resonance imaging [MRI]), clinical neurological examination, and steroid administration. It was assessed as follows: Complete Response (CR): Disappearance of all enhancing tumor (measurable or non-measurable), no corticosteroid use, and neurologically stable or improved. Partial Response (PR): ≥50% reduction in size of enhancing tumor (measurable or non-measurable) for any measurable lesions or definite improvement for any non-measurable lesions, corticosteroid dosage stable or reduced, and neurologically stable or improved. Progressive Disease (PD): ≥25% increase in contrast enhancement for any measurable lesions or definite worsening for any non-measurable lesions, or any new tumor on MRI scans, at an increased dose of corticosteroid, with or without neurologic progression. Clinical or radiological worsening resulting from other than tumor factors were excluded. Stable Disease (SD): All other situations. | Up to 2 years | 
| Relationship Between O6-methylguanine-DNA Methyltransferase (MGMT) Status and Therapy Response: Overall Survival for the MGMT Positive Group | MGMT was measured by immunohistochemistry (IHC). OS was defined as the length of time from the start of treatment that 1/2 of the participants were still alive. OS was calculated by the Kaplan-Meier method. | Up to 2 years | 
| Relationship Between MGMT Status and Therapy Response: Overall Survival for the MGMT Negative Group | MGMT was measured by IHC. OS was defined as the length of time from the start of treatment that 1/2 of the participants were still alive. OS was calculated by the Kaplan-Meier method. | Up to 2 years | 
| Relationship Between MGMT Status and Therapy Response: Overall Survival Rate for the MGMT Positive Group | MGMT was measured by IHC. OS rate was defined as the percentage of participants who were still alive 6, 12, & 18 months after starting study treatment. OS was calculated by the Kaplan-Meier method. | 6, 12, & 18 months | 
| Relationship Between MGMT Status and Therapy Response: Overall Survival Rate for the MGMT Negative Group | MGMT was measured by IHC. OS rate was defined as the percentage of participants who were still alive 6, 12, & 18 months after starting study treatment. OS was calculated by the Kaplan-Meier method. | 6, 12, & 18 months | 
| Relationship Between MGMT Status and Therapy Response: PFS for the MGMT Positive Group | MGMT was measured by IHC. PFS: The length of time during and after treatment that a participant lived with the cancer but it does not get worse. PFS was calculated by the Kaplan-Meier method. | Up to 2 years | 
| Relationship Between MGMT Status and Therapy Response: PFS for the MGMT Negative Group | MGMT was measured by IHC. PFS: The length of time during and after treatment that a participant lived with the cancer but it does not get worse. PFS was calculated by the Kaplan-Meier method. | Up to 2 years |