Temozolomide 12 Cycles Versus 6 Cycles of Standard First-line Treatment in Patients With Glioblastoma.

Study Overview
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Brief Summary
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The purpose of this study is to show if prolonging treatment with temozolomide to 12 cycles improve progression-free survival in patients with glioblastoma included in this study, randomized according to o6-methylguanine-DNA-methyltransferase (MGMT) methylation status and residual disease or not, to receive an additional 6 cycles of temozolomide.

Official Title
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Clinical Trial Phase IIB Randomized, Multicenter, of Continuation or Non Continuation With 6 Cycles of Temozolomide After the First 6 Cycles of Standard First-line Treatment in Patients With Glioblastoma.

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and sign the informed consent document . Age greater than or equal 18. Patients with glioblastoma according to WHO classification (glioblastoma ) who received chemo- radiotherapy and temozolomide -based chemotherapy ( Stupp scheme ) and have completed 6 cycles of adjuvant temozolomide (with or without bevacizumab) in the context of standard treatment without presenting progression of disease. Availability of tumor tissue from the first surgery for centralized histological review , for determining the MGMT study if you have not done in the center of origin. (If they were made in the center of origin the result of the center will be accepted ). Stable dose of dexamethasone in the inclusion never above corticoids dose received in cycle 6 of the adjuvant . Index greater than or equal 60 % Karnofsky. All patients must show no progression of disease in a brain nuclear magnetic resonance (NMR) as defined in RANO established criteria before randomization . Basal NMR study on a maximum of 6 weeks prior to inclusion, in which no progress is observed and is permitted to manage the care 6th cycle ( NMR performed after the 6th cycle of adjuvant is also acceptable as long as no progression was observed). Adequate bone marrow reserve : hematocrit greater or equal 29% , white blood cell> 3,000 , RAN greater or equal 1,500 cells / ul , platelets greater or equal 100,000 cells / ul. Creatinine <1.5 times the upper limit of normal (ULN) of the laboratory performing the analysis. Serum bilirubin <1.5 / ULN; SGOT , SGPT < 2.5 times the upper limit of normal of the laboratory performing the analysis. Serum < 3/ULN alkaline phosphatases . Effective contraceptive method in patients and their partners. Exclusion Criteria: Less than 5 years of any previous invasive neoplasia. In situ cervical carcinoma or basal cell skin carcinoma accepted. Concomitant treatment with other investigational agents (other concomitant bevacizumab) . Presence of any clinically significant gastrointestinal abnormalities that may affect the decision , transit or absorption of study drug , such as the inability to take medication in tablets by mouth. Presence of any psychiatric or cognitive disorder that limits understanding or written informed consent and / or impair compliance with the requirements of this protocol. Concurrent disease that prevents the continuation of temozolomide treatment. Presence of leptomeningeal dissemination. Pregnant or breastfeeding. Positive patients receiving combination antiretroviral therapy in HIV

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Temozolomide<br>Those patients will take 6 additional Temozolomide cycles | Drug: Temozolomide<br> <br> |
| No Intervention: Without treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival at 6 Month | Percentage of patients without progression of disease and time between start of treatment and progression of disease. The progression disease is defined as the time from the date of randomization to the date of progression defined according to the RANO criteria. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Effects | Total number of patients presenting adverse events, stratified by type of event and grade. Adverse Events of special interest: Only relevant differences in toxicity by arm. | Through the whole study. 4 years | 
| Progresion Free Survival Median Values | It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival | Through the whole study. 4 years. The median follow up for each patient was 33.4 months | 
| Overall Survival | Time between start of treatment and death | Through the whole study. 4 years. The median follow up for each patient was 33.4 months | 
| Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status | Median Progression Free Survival depending on treatment arm in patients with MGMT methylation | Through the whole study. 4 years. The median follow up for each patient was 33.4 months | 
| Median Overall Survival (OS) by Arm and MGMT Methylation Status | Median OS depending on treatment arm in patients with methylated MGMT | Through the whole study. 4 years. The median follow up for each patient was 33.4 months | 
| Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity | partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques. | baseline |