Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma
- Conditions
- Astrocytoma, Grade IIIGlioblastoma
- Interventions
- Registration Number
- NCT03224104
- Brief Summary
This is a three parallel cohort, open-labeled, non-randomized, multicenter study. All three cohorts will enroll independently.
- Detailed Description
Group A will be composed of newly-diagnosed, elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and RT.
Group B will be composed of newly-diagnosed, elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.
For both Groups A and B, there will be a classical 3+3 dose escalation and an expansion phase in the study. Up to a total of 24 evaluable patients in Group A and up to a total of 12 evaluable patients in Group B (up to 36 evaluable patients for Groups A and B).
Group C patients will be composed of patients initially diagnosed with IDH1R132H-non-mutant anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT--\>TMZ therapy who will receive TG02.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 71
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A - TG02 + RT Radiation Therapy Elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiation therapy. Group C - TG02 TG02 Patients initially diagnosed with anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT --\> TMZ therapy who will receive TG02. Group B - TG02 + TMZ TG02 Elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide. Group A - TG02 + RT TG02 Elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiation therapy. Group B - TG02 + TMZ Temozolomide Elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.
- Primary Outcome Measures
Name Time Method Progression-free survival at 6 months (PFS-6) 30 months from first patient in Primary endpoint in Group C is Progression-free survival at 6 months (PFS-6) defined by RANO criteria.
Maximum Tolerated Dose (MTD) 27 months from first patient in Primary endpoints in Groups A and B are the determination of the Maximum Tolerated Dose (MTD) and the recommended phase II combination dose. This part is a two-cohort study of the combination of TG02 with hypofractionated RT in patients with tumors with an unmethylated MGMT promoter, or with TMZ in patients with tumors with a methylated MGMT promoter. Up to two dose levels of TG02 will be explored in each group.
- Secondary Outcome Measures
Name Time Method Neurological progression-free survival 30 months from first patient in For group C: neurological progression-free survival (NPFS) based on the Neurologic Assessment in Neuro-Oncology (NANO): median NPFS and NPFS at 6 months (NPFS-6).
Toxicity according CTCAE version 4.0 30 months from first patient in This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.
Molecular markers 30 months from first patient in Correlation of molecular markers including MYC, MCL-1, CDK9 and CDK5 protein levels, and potentially others, with measures of clinical benefit.
Progression-free survival 30 months from first patient in Progression-free survival (PFS) defined by RANO criteria. For groups A and B progression-free survival at 6 months (PFS-6), for group all groups median progression-free survival.
Overall survival (OS) 30 months from first patient in For all groups median overall survival and OS at 9 months (OS-9), for group C additional overall survival at 1 year (OS-12).
Response to treatment 30 months from first patient in For patients with measurable disease after debulking: best overall response distribution (BOR), objective response rate (PR+CR), complete response rate and duration of response (DOR).
For non-surgical patients or patients with surgery for recurrence, but measurable disease thereafter: best overall response distribution (BOR), objective (PR+CR) rate, complete response rate and duration of response (DOR)
Trial Locations
- Locations (10)
UniversitaetsSpital Zurich
🇨🇭Zürich, Switzerland
Universitaetskliniken der Uni Wien - Universitaetsklinikum Wien - AKH uniklinieken
🇦🇹Vienna, Austria
Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone
🇫🇷Marseille, France
Klinikum Der J.W. Goethe Universitaet-Klinik und Poliklinik fur Neurochirurgie
🇩🇪Frankfurt, Germany
Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
🇩🇪Heidelberg, Germany
Universitaetskliniken Regensburg - Universitaetsklinikum Regensburg
🇩🇪Regensburg, Germany
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
🇫🇷Bron, France
CHRU de Lille
🇫🇷Lille, France
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Erasmus MC Cancer Institute - location Daniel den Hoed
🇳🇱Rotterdam, Netherlands