Supramarginal Resection in Glioblastoma

Glioblastoma Clinical Trial

Official title:

Supramarginal Resection in Patients With Glioblastoma: A Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04243005
• Other study ID #: 2019/1046
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: March 2030

Study information

• Verified date: December 2023
• Source: St. Olavs Hospital
• Contact: Asgeir S Jakola, MD, PhD
• Phone: +47 72 57 30 00
• Email: legepost[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gliomas are the most common malignant brain tumor. Glioblastoma, WHO grade IV astrocytoma, is the most common subtype and unfortunately also the most aggressive subtype with median survival in population based cohorts being only 10 months. Extensive surgical resections followed by postoperative fractioned radiotherapy and concomitant and adjuvant temozolomide prolong survival and is the standard treatment.

The investigators think there is significant potential in individualized surgical decision-making in glioblastoma management. The idea that some patients are amendable to radical surgery, while others should be treated more conservatively, is not controversial in other fields of oncology. The current concept in all patients with glioblastoma is "maximum safe resection of the contrast enhancing tumor", but this may in selected cases be extended to simply "maximum safe resection" tailored to the patient and extent of disease at hand.

Densely proliferating tumor cells have been found from at an average of 10 mm beyond the margins of contrast enhancement in high-grade gliomas. There are now several case series, using various definitions of supramarginal resection, but they have in common that they report a benefit of resection with a margin. This potential benefit also comes together with an associated neurological risk, making this approach unethical and simply not feasible in the patients with glioblastoma as a whole.

Objective of this study is: To investigate if resection with a margin, that is significantly beyond the radiological contrast enhancement, improves survival in selected patients with glioblastoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2030
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. A suspected diagnosis of supratentorial glioblastoma by MRI.(A)

2. Indication for surgical treatment and where supramarginal resection is considered possible according to the preoperative imaging. This consideration needs to be verified by two specialists in neurosurgery.

3. Negative work-up for other primary tumor(B)

4. Karnofsky performance status of 70 - 100.

A) If randomized to supramarginal surgery, intraoperative frozen section must conclude with "high-grade glioma" to be able to proceed. Surgery in two sessions is also possible in supramarginal group if there is no intraoperative frozen section available or frozen section indicate another diagnosis, but final histopathology reveals a glioblastoma. In case of surgery in two session, there must be no more than 30 days between procedures. See flow-chart in attachment 1.

B) No suspected primary tumor seen on CT chest, abdomen and pelvis. If relevant symptoms/clinical suspicion also supplement with mammography, dermatologist exam, relevant endoscopies etc.

Exclusion Criteria:

1. Not willing to be randomized.

2. Informed consent not possible (e.g. language barriers, aphasia, cognitive severely impaired).

3. Contrast enhancement volume bilateral OR involving corpus callosum.

4. Contrast enhancement along the ependymal lining of ventricles (contact is however not an exclusion criteria).

5. Contrast enhancement involving several lobes.

6. History of major psychiatric disorder such as psychosis, schizophrenia and/or mood disorder (e.g. depression and bipolar disorder) in need of hospitalization

7. Unfit for participation for any other reason judged by the including physician

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Procedure:
• Supramarginal resection
Aim of supramarginal resection, where a margin of at least 10 mm is considered feasible prior to surgery. The resection is guided by the T2 volume (i.e. zone of edema) where removal of as much as possible of this zone (or beyond) is attempted as long as considered safe
• Conventional surgery
Aim of gross total resection (i.e. removal of contrast enhancing tumor) according to institutional practice. No limit in use of technical adjuncts in this arm.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
Norway	Haukeland University Hospital	Bergen
Norway	Oslo University Hospital, Rikshospitalet	Oslo
Norway	Ullevål University Hospital	Oslo
Norway	University Hospital North Norway	Tromsø
Norway	St Olavs Hospital	Trondheim
Sweden	Sahlgrenska University Hospital,	Göteborg
Sweden	Linköping University Hospital	Linköping
Sweden	Skåne University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm
Sweden	University Hospital of Umeå	Umeå
Sweden	Uppsala University Hospital	Uppsala

Sponsors (20)

Lead Sponsor

Collaborator

St. Olavs Hospital

Haukeland University Hospital, Helsinki University Central Hospital, Karolinska University Hospital, Kuopio University Hospital, Medical University of Vienna, Norwegian University of Science and Technology, Odense University Hospital, Oulu University Hospital, Paracelsus Medical University, Rikshospitalet University Hospital, Sahlgrenska University Hospital, Sweden, Skane University Hospital, Tampere University Hospital, Turku University Hospital, Ullevaal University Hospital, University Hospital of North Norway, University Hospital, Linkoeping, University Hospital, Umeå, Uppsala University Hospital

Countries where clinical trial is conducted

Austria,  Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival; as treated	Accounting for cross-over or failure to achieve predefined surgical aim. "As treated" populations when no margins in supramarginal group and unintended contrast remnant in group aiming at conventional gross-total resection or even if significant supramarginal resection in this group	36 months after the last included patient.
Primary	Overall survival	Overall survival according to intention-to-treat	36 months after the last included patient.
Secondary	Proportion alive	Proportion alive	24 months after randomization.
Secondary	Proportion alive	Proportion alive	36 months after randomization.
Secondary	Neurological function	Neurological assessment in Neuro-Oncology (NANO) Scale is a tool used by healthcare providers to objectively quantify the impairment caused by a tumor within the central nervous system. The NANO is composed of 9 items. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NANO scale score. The maximum possible score is 23, with the minimum score being a 0.	Early postoperative (i.e. prior to radiotherapy) to 36 months
Secondary	Health-related quality of life assessed by EQ-5D 3L	The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.	Early postoperative (i.e. prior to radiotherapy) to 36 months
Secondary	Health-related quality of life assessed by EORTC QLQ C30	The QLQ-C30 is a cancer health-related quality-of-life questionnaire that has been widely used in clinical trials and investigations using PROs for individual patient management. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Most items use a "past week" recall period. Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden.	Early postoperative (i.e. prior to radiotherapy) to 36 months
Secondary	Health-related quality of life assessed by BN20	The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20 is a quality of life assessment specific to brain neoplasms. Consists of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much." Higher score means worse outcome.	Early postoperative (i.e. prior to radiotherapy) to 36 months
Secondary	Neurocognition	The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. Any score of 24 or more (out of 30) indicates a normal cognition. Below this, scores can indicate severe (=9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.	Early postoperative (i.e. prior to radiotherapy) to 36 months
Secondary	Surgical complication	surgical complication grade 3, 4 and 5, assessed using the Dindo-Clavien classification	30 days
Secondary	Proportion with contrast remnant	Resection proportion with contrast remnant	Within 72 hours postoperative
Secondary	Extent of resection, T2/FLAIR remnant	Proportion with remnant in terms of hyper intensity changes in T2/FLAIR	Within 72 hours postoperative
Secondary	Margin of resection	Cavity volume/contrast enhancement volume	Within 72 hours postoperative