Clinical trial NCT02209948: Temozolomide 12 Cycles Versus 6 Cycles of Standard First-line Treatment in Patients With Glioblastoma.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: Grupo Español de Investigación en Neurooncología
Sponsor class: OTHER
First posted: 2014-08-06
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival at 6 Month
timeFrame: 6 month
Secondary outcomes:
measure: Number of Participants With Adverse Effects
timeFrame: Through the whole study. 4 years
measure: Progresion Free Survival Median Values
timeFrame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
measure: Overall Survival
timeFrame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
measure: Median Progression-free Survival (PFS) by Arm and MGMT Methylation Status
timeFrame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
measure: Median Overall Survival (OS) by Arm and MGMT Methylation Status
timeFrame: Through the whole study. 4 years. The median follow up for each patient was 33.4 months
measure: Translational Sub-study - Biomarkers: mutS Homolog 6 (MSH6) Immunoreactivity
timeFrame: baseline
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol/ICO Badalona
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia L'Hospitalet
state: Barcelona
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
state: Mallorca
city: Reus
country: Spain
facility: Hospital Universitario Sant Joan de Reus
state: Tarragona
city: Castelló
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
state: Valencia
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Ciudad Real
country: Spain
facility: Hospital General de Ciudad Real
city: Girona
country: Spain
facility: Hospital Dr. Josep Trueta de Girona
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Germans Trias i Pujol - ICO Badalona
name: Carmen Balañá, M.D.
role: STUDY_CHAIR
affiliation: Hospital Universitario Ramon y Cajal
name: Mª Ángeles Vaz, M.D.
role: STUDY_CHAIR
References:
citation: 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.