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JOURNAL ONKOLOGIE – STUDIE

EF-32 Pivotal, Randomized, Open-label Study of Optune® Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM

Rekrutierend

NCT-Nummer:
NCT04471844

Studienbeginn:
November 2020

Letztes Update:
20.11.2020

Wirkstoff:
-

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
NovoCure GmbH

Collaborator:
-

Kontakt

Studienlocations (3 von 98)

University of North Carolina Brain Tumor Program - UNC Lineberger Comprehensive Cancer Center
27599 Chapel Hill
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Simon Khagi, MD
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Comprehensive Cancer Center of Wake Forest University - Wake Forest Baptist Medical Center
27157 Winston-Salem
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Glenn Lesser, MD
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University of Pittsburgh Medical Center Health System - Center for Neuro-Oncology - Hillman Cancer Institute
15232 Pittsburgh
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Frank Lieberman, MD
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CHUV - Centre hospitalier universitaire vaudois, Department of Clinical Neurosciences and Oncology
Zürich
SwitzerlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Andreas Hottinger, Dr.
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Alle anzeigen

Studien-Informationen

Detailed Description:

Optune® is a medical device that has been approved for the treatment of recurrent and newly

diagnosed glioblastoma (GBM) by the Food and Drug Administration (FDA) in the United States.

Optune® has obtained a CE mark in Europe for recurrent and newly diagnosed GBM.

The current standard of care for GBM includes the addition of Optune® to maintenance

temozolomide (TMZ), following the completion of radiation therapy (RT).

The purpose of the current study is to test if the earlier introduction of Optune®, at the

time of radiation therapy (which is given together with temozolomide), improves clinical

outcomes compared to the standard of care.

The study will randomize 950 subjects equally to one of two treatment arms:

1. Treatment arm I: Patients receive TTFields at 200 kHz to the brain using the Optune®

System together with RT and TMZ, followed by maintenance TMZ concomitant with the

Optune® treatment.

2. Treatment arm II: Patients receive RT and TMZ alone, followed by maintenance TMZ

concomitant with TTFields at 200 kHz to the brain using the Optune®.

All patients are to receive standard RT and TMZ treatment followed by maintenance TMZ

chemotherapy and Optune® according to the current standard of care regimen.

Optune® will continue until second disease progression per RANO Criteria or 24 months (the

earlier of the two) unless any of the treatment discontinuation conditions described under

criteria for patient withdrawal or termination are met.

After surgery or biopsy, subjects that would like to participate will be required to submit

samples of their tumor to a lab for testing. The results of this test will be used for

randomization into the trial.

If the subject is assigned to the treatment group that will start Optune® therapy during

radiation therapy, Optune® therapy will begin within 7 days of enrolling in the study and no

later than the first day of RT and TMZ treatment.

After the initial visit, subjects will continue treatment at home, while pursuing normal

daily routines. Subjects are required to use the device for at least 18 hours a day. Short

breaks in treatment for personal hygiene and other personal needs is allowed. Total usage

time will be recorded and provided to the sponsor.

Subjects will be required to return to the clinic every 4 weeks until study participation

ends. Once every 8 weeks until the tumor potentially returns twice, subjects will have a

contrast MRI of the head and neurological exam performed for the first 6 months of the study

and then at least every three months until a total time period of 24 months.Once every 12

weeks until second disease progression, subjects will also fill out a quality of life

questionnaire.

After the second time the tumor returns, subjects will return to the clinic for one final

visit approximately 30 days after the last treatment with Optune®.

After discontinuing Optune® subjects will be contacted once per month by telephone to answer

basic questions about their health status.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Histologically confirmed diagnosis of GBM according to WHO classification criteria.

2. Age ≥ 22 years in US and Age ≥ 18 years in Ex-US

3. Recovered from maximal debulking surgery, if applicable (gross total resection,

partial resection, and biopsy-only patients are all acceptable)

4. Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2

daily x 5 d, q28 days)

5. Karnofsky performance status ≥ 70

6. Life expectancy ≥ least 3 months

7. Participants of childbearing age must use highly effective contraception. An effective

method of birth control is defined as one that results in a failure rate of less than

1% per year when used consistently and correctly. The Investigator must approve the

selected method, and may consult with a gynecologist as needed.

8. All patients must understand and voluntarily sign an informed consent document prior

to any study related assessments/procedures being conducted.

9. Stable or decreasing dose of corticosteroids for the last 7 days prior to

randomization, if applicable.

10. Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery

11. Women of childbearing potential must have a negative β-HCG pregnancy test documented

within 14 days prior to registration

12. Is able to have MRI with contrast of the brain

Exclusion Criteria:

1. Progressive disease (per investigator's assessment)

2. Infratentorial or leptomeningeal disease

3. Participation in another clinical treatment study during the pre-treatment and/or the

treatment phase of the study

4. Pregnancy or breast-feeding.

5. Significant co-morbidities at baseline which would preclude maintenance RT or TMZ

treatment, as determined by the investigator:

1. Thrombocytopenia (platelet count < 100 x 103/μL)

2. Neutropenia (absolute neutrophil count < 1.5 x 103/μL)

3. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)

4. Significant liver function impairment - AST or ALT > 3 times the upper limit of

normal

5. Total bilirubin > 1.5 x upper limit of normal

6. Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)

7. History of any psychiatric condition that might impair patient's ability to

understand or comply with the requirements of the study or to provide consent

6. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic

devices in the brain, or documented clinically significant arrhythmias.

7. Evidence of increased intracranial pressure (midline shift > 5mm, clinically

significant papilledema, vomiting and nausea or reduced level of consciousness)

8. History of hypersensitivity reaction to TMZ or a history of hypersensitivity to DTIC.

9. Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will

be considered exclusion.

10. Admitted to an institution by administrative or court order.

11. Known allergies to medical adhesives or hydrogel

12. A skull defect (such as, missing bone with no replacement)

13. Prior radiation treatment to the brain for the treatment of GBM

14. Any serious surgical/post-operative condition that may risk the patient according to

the investigator

15. Standard TTFields exclusion criteria include

1. Active implanted medical devices

2. Bullet fragments

3. Skull defects

Studien-Rationale

Primary outcome:

1. Overall Survival (OS) (Time Frame - 5 years):
Survival will be measured from the time of randomization until date patient is alive.



Secondary outcome:

1. Progression Free Survival (PFS) (Time Frame - 5 years):
PFS will be measured from the date of randomization to the date of progression.

2. 1- and 2-year survival rates (Time Frame - 5 years):
The analyses will be performed based on estimated proportions of patients who are on study at 12 and 24 months in both arms of the study.

3. Overall Radiological response (ORR) (Time Frame - 5 years):
The analyses will be performed based on the RANO criteria, and comparison between the rates of response.

4. Next progression-free survival (PFS2) (Time Frame - 5 years):
PFS2 is measure if it is significantly greater in the TTFields and RT and with TMZ arm than in the RT + TMZ followed by TTFields alone arm.

5. Progression-free survival at 6 (PFS6) and 12 months (PFS12) (Time Frame - 5 years):
The analyses will be estimated proportions of patients who are progression-free at 6 and 12 months in both arms of the study.

6. Severity and frequency of adverse events (Time Frame - 5 years):
The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments.

7. Pathological changes in resected GBM tumors following study treatments (Time Frame - 5 years):
Pathological changes in the tumors and also underwent another surgical resection while on the study.

8. Quality of Life EORTC Questionnaire (Time Frame - 5 years):
The analyses will be assessed using the EORTC QLQ C-30 questionnaire with BN-20 (brain symptom) supplement.

9. Dependence of overall survival on TTFields dose at the tumor (Time Frame - 5 years):
Examining the dependence of overall survival on TTFields dose delivered to the tumor bed will be performed in both the treatment and control arms.

10. The NANO scale (Time Frame - 5 years):
The Neurological assessment in Neuro-Oncology will be assessed using the NANO scale questionnaire and per RANO criteria.

Studien-Arme

  • Experimental: Optune® + RT + TMZ for 6 weeks
    Optune® + RT + TMZ for 6 weeks, followed by Optune® + TMZ until the tumor progresses. Optune treatment could be maintained up to 24 months without tumor progression.
  • Active Comparator: RT +TMZ for 6 weeks
    RT +TMZ for 6 weeks followed by Optune® + TMZ until the tumor progresses. Optune treatment could be maintained up to 24 months without tumor progression.

Geprüfte Regime

  • Optune®:
    Optune® is a commercial, portable, battery-operated device intended for continuous home use, which delivers TTFields at a frequency of 200kHz to the brain by means of insulated transducer arrays. The Optune® device produces electric forces intended to disrupt cancer cell division. In treatment arm I, the patient starts Optune® concurrently with RT/TMZ for 6 weeks, followed by Optune® + TMZ until tumor progression. In treatment arm II, the patient starts RT/TMZ for 6 weeks, followed by Optune® + TMZ until tumor progression. The study treatment plan will continue for 24 months, if no tumor progression.

Quelle: ClinicalTrials.gov


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