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

Phase 2

Completed

• Conditions: Glioblastoma
• Interventions: Drug: Temozolomide

• Registration Number: NCT02209948
• Lead Sponsor: Grupo Español de Investigación en Neurooncología

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-08-04
• Study First Submitted QC: 2014-08-05
• Study First Posted: 2014-08-06
• Study Start: 2014-08-22
• Primary Completion: 2019-06
• Study Completion: 2019-06-14
• Results First Submitted: 2020-10-20
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-17
• Last Update Submitted: 2020-12-17
• Results First Posted: 2021-01-12
• Last Update Posted: 2021-01-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 166

Inclusion Criteria

1. Ability to understand and sign the informed consent document .
2. Age greater than or equal 18.
3. 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.
4. 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 ).
5. Stable dose of dexamethasone in the inclusion never above corticoids dose received in cycle 6 of the adjuvant .
6. Index greater than or equal 60 % Karnofsky.
7. All patients must show no progression of disease in a brain nuclear magnetic resonance (NMR) as defined in RANO established criteria before randomization .
8. 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).
9. 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.
10. Creatinine <1.5 times the upper limit of normal (ULN) of the laboratory performing the analysis.
11. 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 .
12. Effective contraceptive method in patients and their partners.

Exclusion Criteria

1. Less than 5 years of any previous invasive neoplasia. In situ cervical carcinoma or basal cell skin carcinoma accepted.
2. Concomitant treatment with other investigational agents (other concomitant bevacizumab) .
3. 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.
4. Presence of any psychiatric or cognitive disorder that limits understanding or written informed consent and / or impair compliance with the requirements of this protocol.
5. Concurrent disease that prevents the continuation of temozolomide treatment.
6. Presence of leptomeningeal dissemination.
7. Pregnant or breastfeeding.
8. Positive patients receiving combination antiretroviral therapy in HIV

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Temozolomide	Temozolomide	Those patients will take 6 additional Temozolomide cycles

Primary Outcome Measures

Name	Time	Method
Progression Free Survival at 6 Month	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Through the whole study. 4 years. The median follow up for each patient was 33.4 months	Time between start of treatment and death
Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity	baseline	partial immunoreactivity of MSH6 in patients by treatment arm. Tumor samples were stained by immuno-histochemical techniques.
Number of Participants With Adverse Effects	Through the whole study. 4 years	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.
Median Overall Survival (OS) by Arm and MGMT Methylation Status	Through the whole study. 4 years. The median follow up for each patient was 33.4 months	Median OS depending on treatment arm in patients with methylated MGMT
Progresion Free Survival Median Values	Through the whole study. 4 years. The median follow up for each patient was 33.4 months	It will be measured following Response assessment in neuro-oncology (RANO) guidelines: progression-free survival
Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status	Through the whole study. 4 years. The median follow up for each patient was 33.4 months	Median Progression Free Survival depending on treatment arm in patients with MGMT methylation

Trial Locations

Locations (20)

Consorcio Hospitalario Provincial de Castellón; 🇪🇸 Castelló, Valencia, Spain

Hospital Universitari Germans Trias i Pujol/ICO Badalona; 🇪🇸 Badalona, Barcelona, Spain

Institut Català d'Oncologia L'Hospitalet; 🇪🇸 L'Hospitalet de Llobregat, Barcelona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Son Espases; 🇪🇸 Palma de Mallorca, Mallorca, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario Sant Joan de Reus; 🇪🇸 Reus, Tarragona, Spain

Hospital Universitario Fundación Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

Hospital Arnau de Vilanova; 🇪🇸 Lleida, Spain

Hospital General de Ciudad Real; 🇪🇸 Ciudad Real, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Universitario Clínico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Dr. Josep Trueta de Girona; 🇪🇸 Girona, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Lucus Augusti; 🇪🇸 Lugo, Spain

Consorcio Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain