Open-Label Pilot Study of OPTUNE® With High Density Transducer Arrays for the Treatment of Recurrent GBM

NCT04492163 | Completed Phase 2

• 1 other identifier: EF-33
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, single arm, historical control pilot study aimed to test the effectiveness and safety of TTFields delivered through high intensity arrays in recurrent glioblastoma. The Optune® System is an investigational , portable, battery operated medical device in this study delivering 200 kHz TTFields to the brain using high intensity transducer arrays for the treatment of patients at the age of 18 years or older with first or second recurrence of Glioblastoma Multiforme (GBM)

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme; Recurrent Glioblastoma; GBM; Treatment; Minimal Toxicity; TTFields; Tumor Treating Fields; NovoCure

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria.

  18 Months

Secondary Outcomes (8)

• Overall Survival (OS)

  18 Months

• Progression Free Survival at 6 months (PFS6)

  18 Months

• 1-year and 2-year survival rates

  24 Months

• Overall radiological response

  18 Months

• Severity and frequency of adverse events

  18 Months

Study Arms (1)

Experimental: TTFields

EXPERIMENTAL

Patients receive continuous TTFields treatment using the Optune® System with high intensity transducer arrays.

Device: TTFields

Interventions

TTFields DEVICE

TTFields treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine. Other Names: • TTFields

Experimental: TTFields

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of GBM according to WHO classification criteria.
• Age ≥ 18 years
• Not a candidate for further radiotherapy or additional resection of residual tumor.
• Patients with first or second radiological disease progression per RANO criteria documented by MRI within 4 weeks prior to starting therapy with the following restriction: disease progression must be either growth of the enhancing lesion or a new lesion.
• Karnofsky performance status ≥ 70
• Life expectancy ≥ least 3 months
• 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.
• All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Treatment start date at least 4 weeks out from brain surgery chemotherapy or irradiation therapy.

You may not qualify if:

• Infratentorial or leptomeningeal disease
• Treatment with Optune® (for newly diagnosed or recurrent disease) prior to enrollment.
• Participation in another clinical treatment study during screening and treatment phase of the study.
• Pregnancy or breast-feeding.
• Significant co-morbidities at baseline, as determined by the investigator:
• Thrombocytopenia (platelet count \< 100 x 103/μL)
• Neutropenia (absolute neutrophil count \< 1 x 103/μL)
• CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
• Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
• Total bilirubin \> 1.5 x upper limit of normal
• Significant renal impairment (serum creatinine \> 1.7 mg/dL, or \> 150 µmol/l)
• 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
• Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
• Admitted to an institution by administrative or court order.

Sponsors & Collaborators

• NovoCure GmbH: lead

Study Sites (1)

Nemocnice Na Homolce

Prague, 150 30, Czechia

Location

Related Publications (12)

• Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.

  PMID: 20231676 BACKGROUND

• Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

  PMID: 29260225 BACKGROUND

• Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.

  PMID: 26658786 BACKGROUND

• Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.

  PMID: 17551011 BACKGROUND

• Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.

  PMID: 19387848 BACKGROUND

• Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.

  PMID: 15126372 BACKGROUND

• Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.

  PMID: 22608262 BACKGROUND

• Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9.

  PMID: 21548832 BACKGROUND

• Mun EJ, Babiker HM, Weinberg U, Kirson ED, Von Hoff DD. Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clin Cancer Res. 2018 Jan 15;24(2):266-275. doi: 10.1158/1078-0432.CCR-17-1117. Epub 2017 Aug 1.

  PMID: 28765323 BACKGROUND

• Giladi M, Munster M, Schneiderman RS, Voloshin T, Porat Y, Blat R, Zielinska-Chomej K, Haag P, Bomzon Z, Kirson ED, Weinberg U, Viktorsson K, Lewensohn R, Palti Y. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells. Radiat Oncol. 2017 Dec 29;12(1):206. doi: 10.1186/s13014-017-0941-6.

  PMID: 29284495 BACKGROUND

• Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, Toms SA, Honnorat J, Chen TC, Sroubek J, David C, Idbaih A, Easaw JC, Kim CY, Bruna J, Hottinger AF, Kew Y, Roth P, Desai R, Villano JL, Kirson ED, Ram Z, Stupp R. Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):495-504. doi: 10.1001/jamaoncol.2017.5082.

  PMID: 29392280 BACKGROUND

• Ballo MT, Urman N, Lavy-Shahaf G, Grewal J, Bomzon Z, Toms S. Correlation of Tumor Treating Fields Dosimetry to Survival Outcomes in Newly Diagnosed Glioblastoma: A Large-Scale Numerical Simulation-Based Analysis of Data from the Phase 3 EF-14 Randomized Trial. Int J Radiat Oncol Biol Phys. 2019 Aug 1;104(5):1106-1113. doi: 10.1016/j.ijrobp.2019.04.008. Epub 2019 Apr 23.

  PMID: 31026557 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Josef Vymazal, MD, DSc

  Nemocnice Na Homolce (Na Homolce Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group assignment

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 30, 2020
• Study Start: July 14, 2020
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: August 16, 2024

Record last verified: 2024-05

Locations

CZ (1)