Clinical Trial Finder

Inclusion Criteria:

1. Age ≥18 years and ≤90 years. 2. Tumor recurrence according to the RANO criteria of a previously diagnosed glioblastoma based on the WHO 2021 classification for glioma. 3. The tumor is suitable for resection (according to neurosurgeon) 4. Written informed consent.

Exclusion Criteria:

1. Tumors of the cerebellum, brainstem, or midline. 2. Medical reasons precluding MRI (e.g., pacemaker) 3. Inability to give written informed consent. 4. Secondary high-grade glioma due to malignant transformation from low-grade glioma. 5. Clinical data unavailable for the newly diagnosed setting

This is an international, multicenter, prospective, cohort study. Eligible patients are operated or receive best oncological treatment with a 1:1 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits). Study patients undergo tumor re-resection or receive best oncological treatment and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) and MRC (Medical Research Council) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. This neurolinguistic test-battery is the result of a consensus between the participating centers. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Overall patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system for comorbidities. Health-related quality of life (HRQoL) will be assessed with the EQ-5D questionnaire and the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study, including follow-up, will be 5 years. The primary study objective is to evaluate the safety and efficacy of re-resection versus best oncological treatment (neurological morbidity and overall survival) in recurrent glioblastoma patients as expressed by NIHSS scores and survival data. Secondary study objectives are to study the overall progressive-free survival (PFS), long-term neurological morbidity (3 months and 6 months postoperatively), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resection versus best oncological treatment as expressed by progression on follow up MRI scans based on the RANO criteria24 for tumor progression; NIHSS scores, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs. Patients will be recruited for the study from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals of the ENCRAM Research Consortium, located in Europe and the United States.

Arms

: Re-resection

Resection of the recurrent tumor

: Best oncological treatment

Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care

Interventions

Procedure: - Re-resection

Resection of the recurrent tumor

Drug: - Temozolomide

Re-challenge Temozolomide chemotherapy

Drug: - Lomustine

Second line chemotherapy with Lomustine

Radiation: - Re-irradiation

Re-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor

Procedure: - Experimental therapy

Experimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)

Other: - Best supportive care

Best supportive care, focused on alleviating symptoms