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

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.

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Ciudad Real, Spain, 13005
    • Hospital General de Ciudad Real
  • Girona, Spain, 17007
    • Hospital Dr. Josep Trueta de Girona
  • Lleida, Spain, 25198
    • Hospital Arnau De Vilanova
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol/ICO Badalona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Institut Català d'Oncologia L'Hospitalet
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Hospital Universitario Fundacion Alcorcon
  • Mallorca
    • Palma de Mallorca, Mallorca, Spain, 07010
      • Hospital Son Espases
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • Hospital Universitario Sant Joan de Reus
  • Valencia
    • Castelló, Valencia, Spain, 12002
      • Consorcio Hospitalario Provincial de Castellon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide; Those patients will take 6 additional Temozolomide cycles	Drug: Temozolomide
No Intervention: Without treatment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Grupo Español de Investigación en Neurooncología
• Investigators: Study Chair: Carmen Balañá, M.D., Hospital Germans Trias i Pujol - ICO Badalona; Study Chair: Mª Ángeles Vaz, M.D., Hospital Universitario Ramón y Cajal

Publications and helpful links

General Publications

• Balana C, Vaz MA, Manuel Sepulveda J, Mesia C, Del Barco S, Pineda E, Munoz-Langa J, Estival A, de Las Penas R, Fuster J, Girones R, Navarro LM, Gil-Gil M, Alonso M, Herrero A, Peralta S, Olier C, Perez-Segura P, Covela M, Martinez-Garcia M, Berrocal A, Gallego O, Luque R, Perez-Martin FJ, Esteve A, Munne N, Domenech M, Villa S, Sanz C, Carrato C. A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01). Neuro Oncol. 2020 Dec 18;22(12):1851-1861. doi: 10.1093/neuonc/noaa107.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2014
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 14, 2019

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 6, 2014

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: GEINO 14-01; 2014-000838-39 (EudraCT Number)