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Phase III randomised trial evaluating chemotherapy early treatment intensification with temozolomide in adults present with a glioblastoma

Phase 3
Recruiting
Conditions
Adults with a de novo glioblastoma
Registration Number
2022-500451-23-00
Lead Sponsor
Centre Oscar Lambret
Brief Summary

To evaluate the impact of intensification with early Temozolomide ) compared to Stupp standard protocol, in terms of Overall Survival (OS)

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
400
Inclusion Criteria

Patient ≥18 years old

planned MGMT analysis (results not mandatory at inclusion but must be further reported in the eCRF)

Written informed consent from patient or the person of trust (“personne de confiance”)

France and Belgium: Patient covered by the French or Belgian “Social Security” regime

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 If the diagnosis is not confirmed, the patient will be withdrawn from study.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) ≤ 14 days (ideally in the first 7 days)

Karnofsky performance status (KPS) ≥ 60%, or KPS <60% only related to glioma-related motor paresis.

Adequate biological functions: neutrophils ≥ 1500/mm3, platelets ≥ 100 000/mm3 independent of transfusion, serum creatinine ≤ 1.5 times ULN; transaminases (ALAT/ ASAT) ≤ 3 times ULN; total bilirubin ≤ 1.5 times ULN (except in case of Gilbert’s disease)

Common toxicity criteria (CTC) non hematological adverse events ≤ Grade 1 (except for alopecia, nausea, vomiting and neurological symptoms)

Females of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 6 months after stopping the study drug.

Standard radiation therapy deemed feasible (60 Gy, 30 fractions)

Time interval of less than 43 days between initial surgery/biopsy and planned start of radiation therapy

Exclusion Criteria

IDH-mutant (IDH1 ou IDH2) astrocytoma (grade 4) or recurrent gliosblastoma (GBM)

Inability to comply with medical follow-up of the trial (geographical, social or psychological reasons)

Person under guardianship or curatorship

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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.

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.

Secondary Outcome Measures
NameTimeMethod
Q-TWiST: Quality-adjusted time without symptoms of disease or adverse event

Q-TWiST: Quality-adjusted time without symptoms of disease or adverse event

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.

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)

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)

Exploratory endpoints: Treatment doses will be computed for each treatment component (radiotherapy & 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 chemoradio

Exploratory endpoints: Treatment doses will be computed for each treatment component (radiotherapy & 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 chemoradio

Total dose of irradiation received and dose-intensity.

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.

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.

Description of the post-progression treatments: nature and duration.

Trial Locations

Locations (19)

Centre Hospitalier Universitaire Amiens-Picardie

🇫🇷

Amiens, France

Centre Leon Berard

🇫🇷

Lyon, France

Cancer Centre Henri Becquerel

🇫🇷

Rouen, France

University Hospitals Pitie Salpetriere Charles Foix

🇫🇷

Paris, France

Centre Hospitalier Pasteur

🇫🇷

Colmar Cedex, France

Timone University Hospital

🇫🇷

Marseille, France

Centre Hospitalier Universitaire De Nice

🇫🇷

Nice, France

Institut De Cancerologie Strasbourg Europe

🇫🇷

Strasbourg, France

Centre Francois Baclesse

🇫🇷

Caen Cedex 5, France

Centre Hospitalier Regional Et Universitaire De Brest

🇫🇷

Brest, France

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Centre Hospitalier Universitaire Amiens-Picardie
🇫🇷Amiens, France
Mathieu BOONE
Site contact
0322088000
Boone.mathieu@chu-amiens.fr

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