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

Primary Purpose

Glioblastoma Multiforme, Recurrent Glioblastoma

Status
Active
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
TTFields and SRS
Sponsored by
Prof. Franciszek Lukaszczyk Memorial Oncology Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma, SRS, GBM, recurrent GBM, recurrence, stereotactic radiosurgery, Radiosurgery, FET-PET, 18F-fluoro-etyl-thyrosine, TTFields, Optune

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Franciszek Lukaszczyk Oncology Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TTFields and SRS based on MRI or FET-PET

Arm Description

All subjects will receive TTFields and radiosurgery plus/minus FET PET imaging to define tumor volume.

Outcomes

Primary Outcome Measures

1-year survival rate
Survival will be measured from date of enrollment until date of death

Secondary Outcome Measures

Radiation necrosis range
The percentage of patients who had radiation necrosis
Progression free survival (PFS)
PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria.
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
Patterns of failure
The analysis will be performed based on location of failure in relation to target volume
Objective response rates
The percentage of patients who had either complete response or partial response per RANO criteria following enrollment

Full Information

First Posted
December 5, 2020
Last Updated
June 27, 2023
Sponsor
Prof. Franciszek Lukaszczyk Memorial Oncology Center
Collaborators
NovoCure GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT04671459
Brief Title
TTFields and Radiosurgery of Recurrent Glioblastoma +/- 18F-Fluoro-Ethyl-Thyrosine
Acronym
TaRRGET
Official Title
A Phase II Trial of Tumor Treating Fields (TTFields) Concomitant With Radiosurgery for the Treatment of Recurrent, Bevacizumab-naïve Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 26, 2020 (Actual)
Primary Completion Date
July 20, 2023 (Anticipated)
Study Completion Date
December 9, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Prof. Franciszek Lukaszczyk Memorial Oncology Center
Collaborators
NovoCure GmbH

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Recurrent Glioblastoma
Keywords
Glioblastoma, SRS, GBM, recurrent GBM, recurrence, stereotactic radiosurgery, Radiosurgery, FET-PET, 18F-fluoro-etyl-thyrosine, TTFields, Optune

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is an open-label, phase II trial enrolling participants with recurrences or progressive tumor, who will be treated with radiosurgery and TTFields. The investigators will attempt to enroll the maximum number of patients and expect to enroll 40 subjects. All subjects will receive TTFields and radiosurgery plus/minus FET PET imaging to define tumor volume.
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TTFields and SRS based on MRI or FET-PET
Arm Type
Experimental
Arm Description
All subjects will receive TTFields and radiosurgery plus/minus FET PET imaging to define tumor volume.
Intervention Type
Combination Product
Intervention Name(s)
TTFields and SRS
Other Intervention Name(s)
Optune, Stereotactic Radiosurgery
Intervention Description
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.
Primary Outcome Measure Information:
Title
1-year survival rate
Description
Survival will be measured from date of enrollment until date of death
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Radiation necrosis range
Description
The percentage of patients who had radiation necrosis
Time Frame
12 months
Title
Progression free survival (PFS)
Description
PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria.
Time Frame
12 moths
Title
Steroid needs until treatment failure
Description
The analysis will be performed based on the steroid doses reported in time of enrollment to date of progression or one year after
Time Frame
12 months
Title
Patterns of failure
Description
The analysis will be performed based on location of failure in relation to target volume
Time Frame
12 months
Title
Objective response rates
Description
The percentage of patients who had either complete response or partial response per RANO criteria following enrollment
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient's written informed consent (IC) obtained at the latest the day after planning MRI; Legal capacity: patient can understand the nature, significance, and consequences of the study; Age ≥18 years (no upper age limit); Karnofsky Performance Score (KPS) ≥ 70; Recurrence of GBM (WHO grade IV) based on RANO criteria or GBM after subtotal resection of recurrence with macroscopic residual tumor; Histological confirmation of GBM at initial or secondary diagnosis; Previous radiotherapy of glioma with a total dose of 59.4 - 60 Gy (single dose 1.8 - 2.0 Gy) and chemotherapy with temozolomide; At least 6 months between the end of the first course of radiotherapy and radiosurgery; 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); Start of TTFields before radiosurgery; Disease free from other cancers for ≥ 5 years; 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: Recent (≤ 4 weeks before IC) histological result showing no tumor recurrence; Previous treatment of GBM with bevacizumab; Chemotherapy or molecular targeted therapies planned before diagnosis of further tumor progression after study intervention 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; Pregnancy, nursing, or patient not willing to prevent a pregnancy during treatment; Known or persistent abuse of medication, drugs or alcohol; Known allergy against the MRI contrast agent gadolinium or the PET tracer 18F-FET or against any of the components; Evidence of increased intracranial pressure (midline shift >5 mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness); Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias. Gross total resection of recurrence confirmed with postoperative MRI and negative FET-PET result Other malignancies ,except for non-melanomatous skin cancers, or carcinoma in-situ of uterus, cervix or bladder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maciej Harat, MD PhD
Organizational Affiliation
Prof. Franciszek Lukaszczyk Memorial Oncology Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Franciszek Lukaszczyk Oncology Center
City
Bydgoszcz
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
IPD and all supporting data will be available upon request.

Learn more about this trial

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

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