TTFields and Radiosurgery of Recurrent Glioblastoma +/- 18F-Fluoro-Ethyl-Thyrosine (TaRRGET)

A Phase II Trial of Tumor Treating Fields (TTFields) Concomitant With Radiosurgery for the Treatment of Recurrent, Bevacizumab-naïve Glioblastoma

All patients will receive TTFields therapy and additionally Stereotactic Radiosurgery . Radiosurgery will be based on MRI and FET-PET or MRI alone. Addition of FET-PET will be preferred option.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma Multiforme; Recurrent Glioblastoma
• Intervention / Treatment: Combination product: TTFields and SRS

Detailed Description

Almost all GBM patients experience recurrent disease. Stereotactic radiosurgery (SRS),at recurrence, has limitations due to the invasive nature of glioblastoma. TTFields may decrease the tumor aggressiveness outside the target area potentially by multiple pathways, including immunogenic cell death and DNA repair inhibition sensitizing to radiation. We hypothesize that combined SRS and TTFields will be complementary, improving outcomes with minimal toxicity.

In this open-label, phase II trial 40 participants with recurrence will be treated with SRS and TTFields, starting in 2020. Recurrence will be defined on FET-PET or MRI using RANO criteria.

All patients will begin treatment within 14 days from baseline imaging evaluation and at maximum 42 days from screening.

The attempt to obtain the Methyl-guanine methyl-transferase (MGMT) gene promoter methylation and IDH1 and IDH2 mutation from primary tumor are made during the study whenever not defined before entering to the study.

TTFields treatment will be initiated as in clinical routine at patients home. Admission to hospital will not be necessary.

SRS must be delivered within 7 days of TTFields start. A 5-day SRS regimen is allowed. TTFields should be interrupted only during SRS. The sample size of the study was calculated for the comparison of survival against a historical control.Overall survival will be stratified by volume, PET-based treatment, SVZ invasion, MGMT methylation status, time to first progression, and TTFields compliance.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland
    • The Franciszek Lukaszczyk Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient's written informed consent (IC) obtained at the latest the day after planning MRI;
2. Legal capacity: patient can understand the nature, significance, and consequences of the study;
3. Age ≥18 years (no upper age limit);
4. Karnofsky Performance Score (KPS) ≥ 70;
5. Recurrence of GBM (WHO grade IV) based on RANO criteria or GBM after subtotal resection of recurrence with macroscopic residual tumor;
6. Histological confirmation of GBM at initial or secondary diagnosis;
7. Previous radiotherapy of glioma with a total dose of 59.4 - 60 Gy (single dose 1.8 - 2.0 Gy) and chemotherapy with temozolomide;
8. At least 6 months between the end of the first course of radiotherapy and radiosurgery;
9. Recurrent tumor visible on FET-PET and/or T1Gd-MRI, with the maximum diameter up to 5 cm by either technique (in case of multifocal tumors, the sum of all diameters must be 5 cm on FET-PET and T1Gd-MRI);
10. Start of TTFields before radiosurgery;
11. Disease free from other cancers for ≥ 5 years;
12. Adequate haematologic, renal and hepatic function (absolute neutrophil count ⩾1000/mm3; haemoglobin ⩾100 g/L platelet count, ⩾100,000/mm3; serum creatinine level ⩽1.7 mg/dL (<150 μmol/L); total serum bilirubin level ⩽ the upper limit of normal and liver-function values, <3 times the upper limit of normal);

Exclusion Criteria:

1. Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence;
2. Previous treatment of GBM with bevacizumab;
3. Chemotherapy or molecular targeted therapies planned before diagnosis of further tumor progression after study intervention
4. Simultaneous participation in other interventional trials which could interfere with this trial and/or participation in a clinical trial within the last thirty days before the start of this study and/or previous participation (randomization) in this study;
5. Pregnancy, nursing, or patient not willing to prevent a pregnancy during treatment;
6. Known or persistent abuse of medication, drugs or alcohol;
7. Known allergy against the MRI contrast agent gadolinium or the PET tracer 18F-FET or against any of the components;
8. Evidence of increased intracranial pressure (midline shift >5 mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness);
9. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
10. Gross total resection of recurrence confirmed with postoperative MRI and negative FET-PET result
11. Other malignancies ,except for non-melanomatous skin cancers, or carcinoma in-situ of uterus, cervix or bladder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TTFields and SRS based on MRI or FET-PET; All subjects will receive TTFields and radiosurgery plus/minus FET PET imaging to define tumor volume.	Combination product: TTFields and SRS; SRS procedure will be delivered within 7 days after start of TTFields therapy . A 5-day SRS regimen is allowed. TTFields should be interrupted in time of SRS and start immediately after.; Other Names: Optune, Stereotactic Radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year survival rate	Survival will be measured from date of enrollment until date of death	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation necrosis range	The percentage of patients who had radiation necrosis	12 months
Progression free survival (PFS)	PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria.	12 moths
Steroid needs until treatment failure	The analysis will be performed based on the steroid doses reported in time of enrollment to date of progression or one year after	12 months
Patterns of failure	The analysis will be performed based on location of failure in relation to target volume	12 months
Objective response rates	The percentage of patients who had either complete response or partial response per RANO criteria following enrollment	12 months

Collaborators and Investigators

• Sponsor: Prof. Franciszek Lukaszczyk Memorial Oncology Center
• Collaborators: NovoCure GmbH
• Investigators: Principal Investigator: Maciej Harat, MD PhD, Prof. Franciszek Lukaszczyk Memorial Oncology Center

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2020
• Primary Completion (Estimated): July 20, 2023
• Study Completion (Estimated): December 9, 2024

Study Registration Dates

• First Submitted: December 5, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: GBM; recurrence; stereotactic radiosurgery; TTFields; Glioblastoma; SRS; Radiosurgery; recurrent GBM; Optune; FET-PET; 18F-fluoro-etyl-thyrosine
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: KB 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD and all supporting data will be available upon request.

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