Adults with a de novo glioblastoma MedDRA version: 20.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TEMODAL (TEMOZOLOMIDE)
Product Name: TEMOZOLOMIDE
Pharmaceutical Form: Capsule
Trade Name: TEMODAL (TEMOZOLOMIDE)
Product Name: TEMOZOLOMIDE
Pharmaceutical Form: Capsule
Sponsors
Centre Oscar Lambret
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Patient =18 years old -Histological diagnosis of de novo GBM (extemporaneous diagnosis or standard pathological examination). In case of extemporaneous diagnosis, the patient can be included. If the diagnosis is not confirmed, the patient will be withdrawn from study. -Time between initial surgery/biopsy and planned start of treatment (if allocated to the experimental arm) = 15 days (ideally in the first 7 days) -Karnofsky performance status (KPS) = 60%, or KPS =65 years) yes F.1.3.1 Number of subjects for this age range 134
Exclusion criteria
Exclusion criteria: -Secondary or recurrent glioblastoma (GBM) -Planned use of tumor-treating electric fields -Planned use of Carmustine implants -Prior malignancy in the last 5 years before inclusion or concomitant -Severe myelosuppression -Known hypersensitivity to any of the study drugs, study drug classes, excipients in the formulation or to dacarbazine (DTIC) -Current or recent treatment with another experimental drug or patients included in a clinical therapeutic trial (in the 30 days prior to inclusion). -Known current viral hepatitis, HIV infection or current active infectious disease -Inability to swallow oral medications or any mal-absorption condition -Pregnant or breastfeeding patients. -Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons) -Person under guardianship or curatorship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the impact of intensification with Temozolomide (early TMZ + prolonged adjuvant TMZ) compared to Stupp standard protocol, in terms of Overall Survival (OS);Secondary Objective: Secondary objectives •To compare safety (hematological and non hematological adverse events) between both arms (intensified protocol vs standard protocol) •To evaluate the efficacy of intensification in terms of progression-free survival (PFS) •To evaluate the relative benefit/risk ratio using the Q-TWiST approach Exploratory objectives •To evaluate the feasibility of intensified treatment by comparing it to that of the standard treatment, in terms of doses received and dose-intensity. •To identify prognostic factors of OS and predictive factors of treatment response (clinical and biological factors, including MGMT methylation). •To describe the type of the progression (local or peri-local, remote in the brain, remote in the meninges) •To describe post-progression treatments. ;Primary end point(s): Overall survival will be defined as time interval from randomization to death whatever the cause. Patients alive will be censored at the date of last news. ;Timepoint(s) of evaluation of this end point: 3,5 years after the beginning of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints •Adverse events occurring from randomization until disease progression will be reported and graded using the NCI-CTCAE v5.0 classification, including those related to the underlying disease or its progression. All AE will be analyzed, and described according to the reported causal relationship. An AE will be classified as Severe AE if grade is equal or higher than 3 for extra-hematological AE and grade 4 for hematological AE. •Progression-free survival will be defined as time interval from randomization to the first occurrence of progression according to RANO criteria as assessed by the treating physician, or death whatever the cause. Patients alive without progressive disease will be censored at the date of last news. There will be no central radiological review. . The type of progression will be collected (local or peri-local, remotely in the brain, remotely in the meninges) •Q-TWiST: Quality-adjusted time without symptoms of disease or toxicity Exploratory endpoints •Treatment doses will be computed for each treatment component (radiotherapy and chemotherapy), and by treatment phase (early TMZ / concomitant TMZ / adjuvant TMZ). Early administration of TMZ is unlikely to result in leucopenia and / or thrombocytopenia, which could prevent or inhibit conventional concomitant standard dose chemoradiotherapy. It could also lead to platelet transfusions or infections. Patients will be notified. The percentage of deliveries of complete chemoradiotherapy treatment (TMZ and radiotherapy) will be compared in both arms. •Total dose of irradiation received and dose-intensity. •Predictive factors of overall survival: the list of studied factors will be defined later. The methylation of the MGMT promoter is mandatory and will be done in each center. Tumor material will be stored in order to study other biomarkers. •Description of the post-progression treatments: nature and duration. ;Timepoint(s) of evaluation of this end | — |
Countries
France
Contacts
Public ContactSponsor Unit
Centre Oscar Lambret
Outcome results
None listed