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

Glioblastoma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02209948
• Other study ID #: GEINO 14-01
• Secondary ID: 2014-000838-39
• Status: Completed
• Phase: Phase 2
• Start date: August 22, 2014
• Est. completion date: June 14, 2019

Study information

• Verified date: December 2020
• Source: Grupo Español de Investigación en Neurooncología
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: June 14, 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Temozolomide

Locations

Country	Name	City	State
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Universitari Germans Trias i Pujol/ICO Badalona	Badalona	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellón	Castelló	Valencia
Spain	Hospital General de Ciudad Real	Ciudad Real
Spain	Hospital Dr. Josep Trueta de Girona	Girona
Spain	Institut Català d'Oncologia L'Hospitalet	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Son Espases	Palma de Mallorca	Mallorca
Spain	Hospital Universitario Sant Joan de Reus	Reus	Tarragona
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Español de Investigación en Neurooncología

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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