Trial Outcomes & Findings for Multi-kinase Inhibitor TG02 (TG02) in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma. (NCT NCT03224104)

Patient registration/enrollment was only accepted from authorized investigators. Patients were registered/enrolled on the EORTC online randomized trials access. After registration and shipment of sample has been done, the central laboratory assessed the o6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status. Based on the MGMT results, patients were allocated to group A or B. In group C, patients were directly enrolled.

In all 3 study groups, only eligible patients were enrolled.

Race and Ethnicity were not collected from any participant.

The primary objective in Groups A and B of the EORTC-1608 study is to establish the Maximum Tolerated Dose (MTD) of TG02 and the recommended phase II dose when combined with either radiotherapy (Group A) or temozolomide (Group B) for glioblastoma treatment. The MTD is the highest dose where no more than one of six patients experiences a Dose Limiting Toxicity (DLT). The study requires a 75% dose intensity for TG02 and the concurrent treatment. The trial uses a two-cohort design to assess TG02 with hypofractionated radiotherapy in patients with an unmethylated MGMT promoter or with temozolomide in those with a methylated promoter. Dose escalation begins at 100 mg TG02 twice weekly. If no DLTs occur in the first three patients, the dose increases to 150 mg. If one patient has a DLT, three more are enrolled at the same dose. If no further DLTs occur, escalation continues. If more than one patient has a DLT, escalation stops, and the previous dose is the MTD.

The primary endpoint for Group C is Progression-free survival at 6 months (PFS-6), assessed by Response Assessment in Neuro-Oncology (RANO) criteria. Complete Response (CR) is defined as the disappearance of all enhancing measurable and nonmeasurable disease for at least 4 weeks. Partial Response (PR) requires at least a 50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions for at least 4 weeks. Stable Disease (SD) is when the patient does not qualify for CR, PR, or progression, with stable nonenhancing lesions on the same or lower dose of corticosteroids. Progression (PD) is defined as at least a 25% increase in the sum of products of perpendicular diameters of enhancing lesions compared to the smallest measurement at baseline or best response, a significant increase in T2/FLAIR lesion, any new lesion, or clear clinical deterioration not attributable to other causes.

Progression-free survival (PFS) is a secondary endpoint for Group C. PFS is defined as the number of days from consent to the date of earliest disease progression based on Response Assessment in Neuro Oncology (RANO) criteria (as determined by the Investigator) or to the date of death, if disease progression does not occur. For all groups, the median PFS will be determined. PFS is measured from the start of treatment until the date of disease progression or death, whichever occurs first. Patients without progression or death will be censored at the last date documented to be alive and progression-free.

Overall Survival (OS) is a secondary endpoint for Group C. OS is defined as the number of days from consent to the date of death due to any cause. If a patient has not died, the data was censored at the last date documented to be alive. For all groups, the median OS was determined. The median OS was extracted from the Kaplan-Meier OS curve,

Objective Response (OR) is a secondary endpoint for Group C. For patients with measurable disease after debulking or non-surgical patients with measurable disease after surgery for recurrence, the best overall response distribution (BOR), objective response rate (PR+CR), complete response rate, and duration of response (DOR) was assessed. The objective response rate is the proportion of patients who achieve a partial response (PR) or complete response (CR), while the complete response rate is the proportion of patients who achieve a CR. The duration of response (DOR) is the time from the first documented response (PR or CR) to the date of disease progression or death, whichever occurs first.

Neurological progression-free survival (NPFS) is a secondary endpoint for Group C. NPFS is defined based on the Neurologic Assessment in Neuro-Oncology (NANO) criteria. NPFS is measured from the date of enrollment in the trial until the date of first neurological progression or death, whichever occurs first. If a patient does not experience neurological progression or death, the data will be censored at the last date of post-baseline neurological assessment. The median NPFS will be determined.