CLINICAL TRIAL / NCT04471844
Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM
- Interventional
- Recruiting
- NCT04471844
Contact Information
- Andre Pauls
EF-32: Pivotal, Randomized, Open-Label Study of Optune® (Tumor Treating Fields, 200kHz) Concomitant With Radiation Therapy and Temozolomide for the Treatment of Newly Diagnosed Glioblastoma
To test the effectiveness and safety of Optune® given concomitantly with radiation therapy (RT) and temozolomide (TMZ) in newly diagnosed GBM patients, compared to radiation therapy and temozolomide alone. In both arms, Optune® and maintenance temozolomide are continued following radiation therapy.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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
- Glioblastomas