Treatment Intensification With Temozolomide in Adults With a Glioblastoma

Study Overview
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Brief Summary
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Due to conflicting data on the optimal moment to start TMZ chemotherapy and the impact of prolongation of the adjuvant phase with TMZ, the ANOCEF (Association des Neuro-Oncologues d'Expression Francophone) group proposes this randomized trial comparing an intensified arm (early TMZ and extended adjuvant TMZ until toxicity, progression or patient refusal) versus the classical EORTC regimen as control (RT and concomitant TMZ started 4-6 weeks after surgery followed by a number of adjuvant TMZ cycles strictly limited to 6) for primary GBM adult patients.

Official Title
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Phase III Randomised Trial Evaluating Treatment Intensification With Temozolomide in Adults With a Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Intensified protocol
* Drug: Stupp protocol


Participation Criteria
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Eligibility Criteria
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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 If the diagnosis is not confirmed, the patient will be withdrawn from study.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 <60% only related to glioma-related motor paresis. Adequate biological functions 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 Written informed consent 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensified protocol<br>Early Temozolomide (TMZ) Concomitant TMZ Adjuvant TMZ Prolonged TMZ | Drug: Intensified protocol<br>* Early Temozolomide (TMZ) 1 cycle (150 mg/m²/ day X 5 days, per os) Started between day 2 and 15 after surgery/ biopsy RT (60 Gy, 2 Gy/fraction) + concomitant TMZ (75 mg/m2/day X 42 days, per os) Started between W4 and W6 after surgery/ biopsy Adjuvant TMZ 6 cycles (150-200 mg/m2 X 5 days /month, per os) Started 1 month after the end of the concomitant TMZ Prolonged TMZ Until progression, intolerance, patient's or physician's decision (150-200 mg/m2 every 4 weeks, per os)<br>|
| Active Comparator: Stupp protocol<br>Concomitant Temozolomide (TMZ) Adjuvant TMZ | Drug: Stupp protocol<br>* RT (60 Gy, 2 Gy/fraction) + concomitant Temozolomide (75 mg/m2/day X 42 days, per os) Started between W4 and W6 after surgery/ biopsy Adjuvant TMZ 6 cycles (150-200 mg/m2 X 5 days /month, per os) Started 1 month after the end of the concomitant TMZ<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | time interval from randomization to death whatever the cause | up to 18 months after recruitment of the last patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | from randomization until disease progression - reported and graded using the NCI-CTCAE v5.0 classification | up to 18 months after recruitment of the last patient | 
| Progression-free survival | 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 | up to 18 months after recruitment of the last patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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temozolomide, Stupp protocol