Effectiveness of MR-guided LITT Therapy in Irresectable Glioblastoma (EMITT) (EMITT)

April 9, 2024 updated by: Radboud University Medical Center

(Cost)Effectiveness of MR-guided LITT Therapy in Patients With Primary Irresectable Glioblastoma: a Prospective Multicenter Randomized Controlled Trial (EMITT)

The aim of this study is to investigate the (cost-)effectiveness of LITT (Laser Interstitial Thermal Therapy) in primary irresectable glioblastoma. Glioblastoma are the most common malignant brain tumors and are, due to their devastating nature and the fact that these tumors occur at a relatively young age (median 59 years), responsible for up to 7% of total life years lost from cancer before the age of 70.

The current treatment of glioblastoma consists of maximal safe surgery combined with adjuvant chemoradiation therapy (CRT). However, despite this aggressive treatment, these patients still face a poor prognosis (median overall survival 14.5 - 18.5 months). In addition to that, around 30% of the patients diagnosed with a glioblastoma are not suitable for surgery. These patients miss the benefit of a resection and face an even worse prognosis (median overall survival 5.1 months).

The primary aim of this project is to investigate whether laser therapy combined with CRT improves overall survival, without compromising quality of life, in comparison with CRT alone in patients with primary irresectable glioblastoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

RATIONALE: Glioblastoma (GBM) is the most common primary brain tumor with about 1000 new patients facing this diagnosis each year in the Netherlands alone. It is also one of the most devastating malignancies and due to relatively young age at presentation (median 59 years), GBMs are responsible for up to 7% of total life years lost from cancer before the age of 70. Despite many efforts, patients with glioblastoma face a poor prognosis, with 2-year survival less than 20%. Current standard of care includes maximal safe surgical resection followed by adjuvant chemoradiation therapy (CRT). Subtotal and gross total resection have been associated with significantly longer survival (median OS: 14.5-18.5 months; RR: 0.71-0.84) 6,7, but in 30% of patients surgery is not feasible. These patients miss the benefit of surgical resection and with CRT alone have a profoundly worse survival (median 5.1 months). Laser interstitial thermal therapy (LITT) is recently growing as a minimally invasive alternative to treat brain tumors. Multiple studies have shown the application of LITT in newly diagnosed and recurrent glioblastoma, in radiotherapy and chemotherapy resistant metastases or in tumors in difficult accessible locations, with promising initial results. A recent systematic review of current phase I/II studies in patients with newly diagnosed irresectable glioblastoma who received LITT yields a mean survival of 10.2 months, i.e. twice as long as with CRT alone (5.1 months). However, there is currently no high-quality prospective evidence directly comparing LITT with standard of care, precluding any conclusions on (cost-)effectiveness. After conducting a pilot study at Radboud University Medical Center to locally confirm safety and feasibility of LITT in patients with irresectable glioblastoma, we propose a prospective multicenter randomized controlled study to evaluate (cost-)effectiveness of this technique.

OBJECTIVE: The primary objective is to prove an improvement in survival without substantially compromising quality-of-life (QoL) in patients with primary irresectable glioblastoma (GBM) treated with LITT plus chemoradiation therapy (CRT) vs. CRT alone.

STUDY DESIGN: Prospective multicenter randomized controlled trial. Study population: Adult (>18 years old) patients with a radiologically suspected diagnosis of primary glioblastoma not amenable for surgical resection.

INTERVENTION: Patients will be randomized to receive either (i) biopsy and LITT, followed by standard CRT or (ii) biopsy alone, followed by standard CRT.

MAIN STUDY PARAMETERS/ENDPOINTS: The primary endpoints are overall survival (OS) and quality-of-life (QoL) using QLQ-C30+BN20 questionnaire 5 months after randomization.

Secondary endpoints are disease-specific and progression-free survival (PFS), generic QoL using EQ5D-5L and QLQ-C30+BN20, complication rates, tumor volume response, effects on adjuvant treatment and costs.

NATURE AND EXTENT OF THE BURDER AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS: We hypothesize that the addition of LITT provides patients with an irresectable glioblastoma a relevant survival benefit without compromising their quality of life as compared to current standard treatment. LITT has been shown to carry limited risk of post-operative complications, mostly reversible, and has been associated with fast recovery post-treatment. The main risks associated to the procedure are bleeding, brain edema, neurological deterioration, operation site infection, epilepsy. The results of our near-finished pilot study are showing that the procedure seems to be safe and feasible.

Study Type

Interventional

Enrollment (Estimated)

238

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Amsterdam Medical Center
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Maastricht, Netherlands
        • Maastricht University Medical Center
      • Nijmegen, Netherlands
        • Radboud University Medical Center
      • Rotterdam, Netherlands
        • Erasmus Medical Center
      • Tilburg, Netherlands
        • Elisabeth Tweesteden Ziekenhuis
      • Utrecht, Netherlands
        • University Medical Center Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Informed consent, age >18 years
  • Suspected glioblastoma
  • Supratentorial localization
  • Patient is not amendable for surgical resection as decided by the tumor board
  • Safe trajectory/trajectories possible for ablation of at least 70% of the tumor, avoiding eloquent structures
  • Karnofsky Performance Status (KPS) >=70

Exclusion Criteria:

  • Contra-indication for general anesthesia or MRI
  • Non-glioblastoma diagnosis on pathology analysis
  • No final pathology available
  • Pregnancy
  • Insufficient command of the Dutch language by the patient or a family member, making it impossible to fill in the questionnaires

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Control group (biopsy group)
Standard of care: biopsy + adjuvant treatment
Procedure: Biopsy
A sample of tissue from the tumor is obtained to confirm the diagnosis.
Experimental: Intervention group (LITT group)
Biopsy + LITT + adjuvant treatment
Procedure: Laser Interstitial Thermal Therapy (LITT)
LITT is a minimally invasive neurosurgical procedure in which a laser catheter is placed into the tumor and warms the tumor to such an extent that tumor tissue is destroyed. LITT is performed under MR-guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Depending on which event occurs first: either when a study participant dies or at the end of the trial (61 months).
Percentage of patients still alive for a given period of time after randomization.
Depending on which event occurs first: either when a study participant dies or at the end of the trial (61 months).
Health Related Quality of Life (HR-QoL)
Time Frame: At 5 months after randomization
QoL measured with the QLQ-C30BN20 at 5 months after randomization.
At 5 months after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Costs
Time Frame: At 1, 2, 3, 4, 5, 6, 12, 18, 30, 42 and 54 months after randomization.
Use of care and health-related costs measured using costs questionnaires.
At 1, 2, 3, 4, 5, 6, 12, 18, 30, 42 and 54 months after randomization.
Ablation rate
Time Frame: Using the MRI made right after LITT procedure
Measuring the expected ablation rate.
Using the MRI made right after LITT procedure
Progression Free Survival (PFS)
Time Frame: During the entire study period, estimated 18 months for each patient
The length of time during and after the treatment of the disease that a patient lives with the disease but it does not get worse.
During the entire study period, estimated 18 months for each patient
Disease Specific Survival (DSS)
Time Frame: During the entire study period, estimated 18 months for each patient
The percentage of patients who have not died from glioblastoma.
During the entire study period, estimated 18 months for each patient
Complication rate
Time Frame: During the entire study period, estimated 18 months for each patient
Registration of complications in both study groups.
During the entire study period, estimated 18 months for each patient
Overall survival since intervention
Time Frame: During the entire study period, estimated 18 months for each patient
Percentage of patients still alive for a given period of time after surgery.
During the entire study period, estimated 18 months for each patient
Tumor volume response
Time Frame: Using the MRI made right after LITT procedure
Response of tumor tissue to LITT.
Using the MRI made right after LITT procedure
Effects of LITT on adjuvant treatment
Time Frame: During the entire study period, estimated 18 months for each patient
Effects of LITT on the effect of adjuvant treatment assessed by tumor response to chemotherapy and radiotherapy on follow-up MRI.
During the entire study period, estimated 18 months for each patient
General Quality of Life
Time Frame: At randomization, 72 hours after surgery, 1, 2, 3, 4, 5, 6, 12, 18, 30, 42 and 54 months after randomization.
QoL measured with the QoL questionnaires.
At randomization, 72 hours after surgery, 1, 2, 3, 4, 5, 6, 12, 18, 30, 42 and 54 months after randomization.
Longitudinal effects
Time Frame: During the entire study period, estimated 18 months for each patient.
Changes attributable to aging during the study period. Longitudinal effects will be assessed using mixed model analysis.
During the entire study period, estimated 18 months for each patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

UMC Utrecht
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch National Health Care Institute

Investigators

  • Principal Investigator: Mark ter Laan, MD, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 8, 2022

Primary Completion (Estimated)

October 31, 2025

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

March 23, 2022

First Submitted That Met QC Criteria

April 1, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL79202.091.21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared with other researchers. All data will be made findable and shared for reuse and/or verification. Restrictions on data sharing only apply to MRI images due to privacy. Metadata will be published in a data repository (Radboud Data Repository). This way the data is findable. When desired, external researchers can request our data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Primary Glioblastoma

Clinical Trials on Biopsy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Armenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe