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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Glioblastoma Multiforme; Glioblastoma, IDH-wildtype; Glioblastoma Multiforme, Adult
• Intervention / Treatment: Procedure: Tumor resection; Behavioral: Palliative Care; Procedure: Tumor biopsy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 1015

Contacts and Locations

• Study Contact: Name: Jasper Gerritsen, MD PhD; Phone Number: 31107036130; Email: j.gerritsen@erasmusmc.nl
• Study Contact Backup: Name: Arnaud Vincent, MD PhD; Phone Number: 31107034211; Email: a.vincent@erasmusmc.nl

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • University Hospital Leuven
    • Contact: Steven De Vleeschouwer, MD PhD
• Germany
  • Heidelberg, Germany
    • Recruiting
    • University Hospital Heidelberg
    • Contact: Christine Jungk, Dr. med.
  • Bavaria
    • Munich, Bavaria, Germany, 74076
      • Not yet recruiting
      • Technical University Munich
      • Contact: Arthur Wagner, MD PhD
• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus Medical Center
      • Contact: Jasper Gerritsen, MD PhD
    • The Hague, Zuid-Holland, Netherlands, 2512 VA
      • Recruiting
      • Haaglanden Medical Centre
      • Contact: Marike Broekman, MD PhD
• Switzerland
  • Bern, Switzerland, 3010
    • Not yet recruiting
    • INSELSPITAL Universitätsspital Bern
    • Contact: Philippe Schucht, MD PhD
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Mitchel Berger, MD PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Brian Nahed, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

1. Age ≥18 years and ≤90 years
2. Tumor diagnosed as HGG (WHO grade III/IV) on MRI as assessed by the neurosurgeon
3. Written informed consent

Exclusion Criteria:

1. Tumors of the cerebellum, brainstem or midline
2. Inability to give written informed consent
3. Secondary high-grade glioma due to malignant transformation from low-grade glioma
4. 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tumor biopsy	Procedure: Tumor biopsy; Tumor biopsy
Palliative Care; Best supportive care without surgical intervention	Behavioral: Palliative Care; Best supportive care without surgical intervention; Other Names: Best Supportive Care
Tumor resection; Maximal safe resection of the tumor	Procedure: Tumor resection; Maximal safe resection of the tumor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jasper Gerritsen
• Collaborators: Massachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University of California, San Francisco; University Hospital Heidelberg; Technical University of Munich; Haaglanden Medical Centre; Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Jasper Gerritsen, MD PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 18, 2023
• First Submitted That Met QC Criteria: November 18, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 18, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Survival; Quality of life; Palliative care; Biopsy; Glioblastoma; Resection; Best supportive care
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: MEC-2020-0812-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No