C71.2
Conditions
Interventions
Group 1: Anterior Temporal Lobectomy (ATL): ATL is a highly standardized surgical procedure commonly performed in patients with pharma-coresistant temporal lobe epilepsy. The dorsal extent of the neoc
Sponsors
Universitätsklinikum Bonn (AöR)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Suspected glioblastoma with contrast-enhancement in preoperative MRI 2. Diffuse high-grade glioma in frozen section procedure, newly diagnosed 3. Tumor localization of the contrast-enhancing lesion on MRI in the temporal lobe: non-dominant side (right hemisphere in right-handed patients, or left-handed patients after testing for dominance): within 6.5 cm from the temporal pole OR dominant side (left hemisphere in right-handed patients, all left-handed patients unless additional testing for dominance performed): within 4.0 cm from the temporal pole as determined dorsally along the Sylvian fissure. Explanation: In the case of right-handedness, the left hemisphere is considered the dominant hemisphere. For left-handed patients, the domi-nant hemisphere is uncertain. Consequently, the extent of resection for left-handed patients within the study should remain within 4.0 cm from the temporal pole for the ATL approach. If additional diagnostic procedures confirm the non-dominant hemisphere (e.g., Wada test, functional MRI, functional transcranial Doppler ultrasonography, magnetoencephalography, or awake mapping methods), the resection boundary may be ex-tended to 6.5 cm at the discretion of the treating neurosurgeon. 5. Macroscopic complete resection (no remaining contrast-enhancing tumoral lesion on early postoperative MRI) is achievable (decision of the treating neurosurgeon) 6. In case further T1-contrast-enhancing and/or T2 and/or FLAIR lesions are detected beyond the resection margins (6.5 cm on the non-dominant side and 4.0 cm on the dominant side), these lesions are not attributed to the tumor (except perifocal edema) but to other conditions according to the local treating neurosurgeon Explanation: Vascular pathologies or other T1-contrast-enhancing lesions that are not attributable to the tumor beyond and inside the resection margins, as well as FLAIR and/or T2 lesions attributable to peritumoral edema do not lead to the exclusion from the study. However, T1-contrast enhancing lesions beyond the resection margins that are attributable to the tumor and multifocal gliomas do lead to an exclusion from the study (for definition of multifocal glioma see 7.3.) 7. KPS = 70% 8. Estimated life expectancy of at least 6 months 9. Written informed consent 10. Cognitive state to understand the rationale and necessity of study therapy and procedures 11. Patient compliance and geographic proximity that allow adequate follow-up 12. For patients with childbearing potential: negative serum pregnancy test (beta-HCG) at baseline visit, patient’s commitment to use an approved contraceptive method during the trial and for 3 months after (Pearl index 1500/µl - platelets = 100000/µl - haemoglobin = 10 g/dl Adequate liver function: - bilirubin < 1.5 times above upper limit of normal range (ULN) - alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/ALAT) < 3 times ULN Adequate renal function: - creatinine < 1.5 times ULN 14. Adequate blood clotting: PTT not exceeding the upper limit of normal range and INR <1.5; in case of intake of anticoagulant medication or platelet function inhibitors, the coagulation analysis must show no detectable effect in specific blo
Exclusion criteria
Exclusion criteria: 1. The dorsal extent of the gadolinium-enhancing tumor reaches more than 6.5 cm measured from the temporal pole dorsally along the Sylvian fissure on the non-dominant side or more than 4.0 cm on the dominant side 2. The extent of GTR is projected to closely approximate that of ATL based on preoperative MRI findings (at the discretion of the treating neurosurgeon) Explanation: This applies if the gadolinium-enhancing tumor components comprise about =90% of the ATL volume, effectively making the extent of GTR equivalent to that of ATL 3. Temporal tumor with gadolinium-enhancing infiltration of further lobi and/or multifocal tumor Explanation: Multifocal tumor is defined as two or more lesions within the same hemisphere but separated by white matter tracts 4. Prior malignancy (unless adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer), unless the prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence 5. Prior chemotherapy, systemic or local treatment with DNA-damaging agents, tyrosine kinase inhibitors or anti-angiogenic agents for any cancer 6. Prior radiotherapy (RT) to the brain 7. Active infection and infections preventing surgery and/or further chemotherapy (at the discretion of the investigator) 8. Conditions with increased risk for intraoperative and/or perioperative bleeding Explanation: Patients with pro- or anticoagulant coagulation disorders may participate in the study if, after consultation with a coagulation specialist or at the discretion of the neurosurgeon, the coagulation status has been optimized. Study participation is not possible for patients on anticoagulation or antiplatelet therapy if the medication cannot be discontinued prior to surgery and at least 1 week postoperatively (e.g., for high cardiovascular risk patients), or the relevant coagulation analysis (as indicated in the inclusion criteria) does not indicate normal coagulation status at time of surgery. 9. Female patients who are pregnant or breastfeeding or patients with childbearing potential who do not commit to use an approved contraceptive method during the trial and for 3 months after (Pearl index < 1%) 10. History of disease with poor prognosis (e.g., severe heart failure) with an estimated life-expectancy < 6 months 11. Unable to undergo contrast-enhanced MRI 12. Any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up scheduled visits (at the discretion of the investigator) 13. Patients not capable of giving consent 14. Patients incapacitated and unable to understand the nature, scope, significance and consequence of this clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) in the modified intention to treat (mITT) population of patients with glioblastoma, CNS WHO grade 4, IDHwt; in case of significant OS differences, the patient-reported QoL domain “global health status” (EORTC QLQ-C30 questionnaire) is the co-primary endpoint. Overall superiority of ATL requires significantly prolonged OS and non-inferiority regarding the development of the global health status over time in the mITT population | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. OS in the population of all patients randomized in the trial (ITT population) and in the per protocol (PP) population. The QoL domain “global health status” (EORTC QLQ-C30 questionnaire will serve as a co-endpoint in analogy to the description of the primary endpoint 2. PFS as measured from the day of randomization until diagnosis of progressive disease determined by MRI (RANO 2.0 criteria) will be analyzed in the ITT, the mITT and the PP-population 3. Separate exploratory OS and PFS analysis of all patients with IDHmut glioma Further secopndary endpoints will be analyzed in the mITT population: •QoL (six preferred domains of the EORTC-QLQ-C30 and BN20 questionnaires: global health status, physical functioning, social functioning, cognitive functioning, communication deficit, motor dysfunction) •All other domains of the EORTC-QLQ-C30 and BN20 question-naires •PFS as measured from the day of randomization until diagnosis of progressive disease determined by MRI (RANO 2.0 criteria) in the mITT population and, separately as an explorative analysis, in the group of patients with IDHmut glioma •KPS, modified Rankin Scale (mRS) •Neurocognitive functioning outcome determined by the Bonner Lesion Tracking Test (BLTT+) •Seizure outcome determined by the International League Against Epilepsy (ILAE) classification Safety Endpoints, to be analyzed in the safety population comprizing all patients randomized in the trial: •mRS: in an Interim Safety Analysis, the DSMB will have to decide on the continuation of the trial if 6 months after inclusion of 57 pa-tients a significant difference between the arms regarding the rate of patients with mRS 4-6 (timepoint: 6 months after each individual randomization) is observed; mRS is also monitored throughout the trial •Periprocedural adverse events as measured by Patient Safety Indi-cators (PSIs) and specific cranial-surgery-related complications (CSCs) until 90 days after randomization •Adverse Events (AEs) until 30 d | — |
Countries
Austria, Germany, Switzerland
Contacts
Public ContactRafael Struck
Universitätsklinikum Bonn (AöR), Studienzentrale des Studienzentrum Bonn
Outcome results
None listed