The PALSUR-study: Palliative Care Versus Surgery in High-grade Glioma Patients (ENCRAM 2203)

Study Overview
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Brief Summary
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There is no consensus on the optimal treatment of patients with high-grade glioma, especially when patients have limited functioning performance at presentation (KPS ≤70). Therefore, there are varied practice patterns around pursuing biopsy, resection, or palliation (best supportive care). This study aims to characterize the impact of palliative care versus biopsy versus resection on survival and quality of life in these patients. Also, it will aim to determine if there is a subset of patients that benefit the most from resection or biopsy, for which outcome, and how they could be identified preoperatively. This study is an international, multicenter, prospective, 3-arm cohort study of observational nature. Consecutive HGG patients will be treated with palliative care, biopsy, or resection at a 1:3:3 ratio. Primary endpoints are: 1) overall survival, and 2) quality of life at 6 weeks, 3 months and 6 months after initial presentation based on the EQ-5D, EORTC QLQ C30 and EORTC BN 20 questionnaires. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

Detailed Description
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Trial design This is an international, multicenter, prospective, observational, 3-arm cohort study (registration: clinicaltrials.gov ID number TBA). Eligible patients are treated with either palliative care, biopsy, or resection with a 1:3:3 ratio with a sequential computer-generated random number as subject ID. Study objectives The primary study objective is to evaluate safety and efficacy of palliative care versus surgery in HGG patients as measured by overall survival (OS) and quality of life questionnaires (QLQ C30, EORTC QLQ BN20, EQ 5D). The primary outcomes are 1) overall survival (OS) defined as time from diagnosis to death from any cause; 2) proportion of patients with health-related quality of life deterioration of 10 points or more in the EORTC QLQ C30 questionnaire or EORTC QLQ BN20 questionnaire at 3 months after outpatient clinic visit. Study setting and participants Patients will be recruited from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals, located in Europe and the United States. The study is carried out by centers from the ENCRAM Consortium. Study patients are allocated to either the supramaximal or maximum safe resection group and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months. Patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system. Health-related quality of life (HRQoL) will be assessed with the EORTC QLQ C30, EORTC QLQ BN20 and EQ 5D questionnaires. Overall survival will be assessed at 6 months postoperatively. We expect to complete patient inclusion in 4 years. The estimated duration of the study (including follow-up) will be 5 years.

Official Title
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The PALSUR-study: Palliative Care Versus Surgery in High-grade Glioma Patients (ENCRAM 2203)

Conditions
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Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype, Glioblastoma Multiforme, Adult

Intervention / Treatment
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* Behavioral: Palliative Care
* Procedure: Tumor biopsy
* Procedure: Tumor resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤90 years Tumor diagnosed as HGG (WHO grade III/IV) on MRI as assessed by the neurosurgeon Written informed consent Exclusion Criteria: Tumors of the cerebellum, brainstem or midline Inability to give written informed consent Secondary high-grade glioma due to malignant transformation from low-grade glioma Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Palliative Care<br>Best supportive care without surgical intervention | Behavioral: Palliative Care<br>* Best supportive care without surgical intervention<br>* Other names: Best Supportive Care;|
| Tumor biopsy<br>Tumor biopsy | Procedure: Tumor biopsy<br>* Tumor biopsy<br>|
| Tumor resection<br>Maximal safe resection of the tumor | Procedure: Tumor resection<br>* Maximal safe resection of the tumor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from diagnosis to death from any cause | Up to 5 years postoperatively | 
| Quality of life at 3 months (EORTC QLQ C30) | Quality of life as assessed by the EORTC QLQ C30 questionnaire | 3 months postoperatively | 
| Quality of life at 3 months (EORTC QLQ BN20) | Quality of life as assessed by the EORTC QLQ BN20 questionnaire | 3 months postoperatively | 
| Quality of life at 3 months (EQ-5D) | Quality of life as assessed by the EQ-5D questionnaire | 3 months postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life at 6 weeks (EORTC QLQ C30) | Quality of life as assessed by the EORTC QLQ C30 questionnaire | 6 weeks postoperatively | 
| Quality of life at 6 weeks (EORTC QLQ BN20) | Quality of life as assessed by the EORTC QLQ BN20 questionnaire | 6 weeks postoperatively | 
| Quality of life at 6 weeks (EQ-5D) | Quality of life as assessed by the EQ-5D questionnaire | 6 weeks postoperatively | 
| Quality of life at 6 months (EORTC QLQ C30) | Quality of life as assessed by the EORTC QLQ C30 questionnaire | 6 months postoperatively | 
| Quality of life at 6 months (EORTC QLQ BN20) | Quality of life as assessed by the EORTC QLQ BN20 questionnaire | 6 months postoperatively | 
| Quality of life at 6 months (EQ-5D) | Quality of life as assessed by the EQ-5D questionnaire | 6 months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palliative care, Best supportive care, Biopsy, Resection, Quality of life, Survival, Glioblastoma