NovoTTF-200A and Temozolomide Chemoradiation for Newly Diagnosed Glioblastoma

NCT03232424 | Completed Phase 1 DMC FDA Device

• 1 other identifier: Pro2017-0087
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective single arm trial designed to study the safety, feasibility and preliminary efficacy of a medical device, NovoTTF-200A used concomitantly with standard adjuvant treatment for newly diagnosed glioblastoma.

Conditions

Glioblastoma, Adult

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Safety and tolerability of combined modality treatment with radiotherapy, temozolomide and NovoTTF-200A based upon the incidence and severity of adverse events.

  24 months

Secondary Outcomes (4)

• Overall survival time

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months

• Progression free survival at 6 months

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

• Quality of life assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ-C30)

  24 months

• Quality of life assessed using a European Organization for Research and Treatment of Cancer (EORTC) Brain Cancer questionnaire (BN20)

  24 months

Study Arms (1)

NovoTTF-200A + Temozolomide Chemoradiation

EXPERIMENTAL

NovoTTF-200A, concomitant with radiotherapy and temozolomide, as front-line therapy for glioblastoma

Device: NovoTTF-200A; Drug: Temozolomide; Radiation: 3D conformal or intensity modulated radiation therapy (IMRT)

Interventions

NovoTTF-200A DEVICE

* Begins the day prior to radiotherapy start and continues until the end of temozolomide maintenance cycle #2 or until evidence of disease progression or unacceptable toxicity. * Arrays are removed immediately prior to radiotherapy and replaced immediately thereafter.

Also known as: Optune

NovoTTF-200A + Temozolomide Chemoradiation

Temozolomide DRUG

Concomitant phase: * 75 mg/m2 per day for 42 days concomitant with radiotherapy. * Begins 1 day prior to XRT start. Maintenance phase: * Begins 4 weeks after concomitant phase completion (+/- 1 week). * Each cycle is 28 days (5 days of drug treatment followed by 23 days without). * Cycle 1: 150 mg/m2 once daily for the first 5 days of each treatment cycle. * Subsequent cycles: daily dose increased to 200 mg/m2, if the CTC non-hematologic toxicity for Cycle 1 is Grade ≤ 2 (except for alopecia, nausea and vomiting), absolute neutrophil count (ANC) is ≥ 1.5 x 109/L, and the platelet count is ≥ 100 x 109/L. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs.

NovoTTF-200A + Temozolomide Chemoradiation

3D conformal or intensity modulated radiation therapy (IMRT) RADIATION

Radiotherapy will commence 4 weeks after the definitive surgical procedure (+/- 1 week), to a total dose of 54.0 - 60.0 Gy, delivered in 1.8 - 2.0 Gy fractions over 6 - 7 weeks. XRT target volumes will be determined utilizing all available imaging studies that best delineate extent of disease. Fusion image registration for treatment planning will be utilized as possible. Either 3D conformal or intensity modulated radiation therapy (IMRT) will be utilized.

NovoTTF-200A + Temozolomide Chemoradiation

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed GBM using WHO criteria.
• Age ≥ 18 years
• KPS ≥ 70
• Life expectancy of at least 3 months.
• Sexually active participants must agree to the strict use of barrier contraception.
• Patients must be able to understand the investigational nature of the study and provide informed consent.
• Adequate hematologic function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ) ≥ 100 x 109/L
• Hemoglobin ≥ 10 g /dL
• Adequate liver function
• Total bilirubin ≤ 1.5 x ULN
• AST and ALT ≤ 2.5 x ULN
• Adequate renal function
• a. Creatinine ≤ 1.25 x ULN

You may not qualify if:

• Active participation in another clinical treatment trial. Concomitant protocols for data or tissue collection without intervention are permitted.
• Any prior treatment for GBM aside from surgery, including carmustine wafers.
• Women who are pregnant or nursing.
• Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation, NovoTTF-200A device use or interfere with interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial. This includes but not limited to:
• Patients with inadequately healed surgical incisions or other dermatologic scalp toxicity at baseline (grade 2 or higher, as defined in Section VIII) upon which transducer leads may require placement.
• Known HIV or other immunosuppressive disease, chronic hepatitis B or hepatitis C
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol.
• Implanted pacemaker, programmable shunt, cardiac defibrillator, deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
• Infratentorial glioblastoma.
• Past hypersensitivity reaction to temozolomide or DTIC.
• Psychiatric illness that compromises the informed consent process, at the discretion of the investigator.
• Inability or unwillingness to return for required visits.
• Previous cytotoxic therapy within the last 5 years.
• Inability to begin temozolomide concomitant to radiation therapy, for reasons 4 or 7 above.

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• NovoCure Ltd.: collaborator

Study Sites (1)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (28)

• Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.

  PMID: 19269895 BACKGROUND

• Polk C. Therapeutic applications of low-frequency sinusoidal and pulsed electric and magnetic fields. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1404-1416.

  BACKGROUND

• Palti Y. Stimulation of internal organs by means of externally applied electrodes. J Appl Physiol. 1966 Sep;21(5):1619-23. doi: 10.1152/jappl.1966.21.5.1619. No abstract available.

  PMID: 5923236 BACKGROUND

• Bassett CA. The development and application of pulsed electromagnetic fields (PEMFs) for ununited fractures and arthrodeses. Clin Plast Surg. 1985 Apr;12(2):259-77.

  PMID: 3886262 BACKGROUND

• Elson E. Biologic Effects of radiofrequency and microwave fields: in vivo and in vitro experimental results. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1417-1423.

  BACKGROUND

• Chou CK. Radiofrequency hyperthermia in cancer therapy. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1424-1430.

  BACKGROUND

• Takashima S, Schwan HP. Alignment of microscopic particles in electric fields and its biological implications. Biophys J. 1985 Apr;47(4):513-8. doi: 10.1016/S0006-3495(85)83945-X.

  PMID: 3986280 BACKGROUND

• Zimmermann U, Vienken J, Pilwat G. Rotation of cells in an alternating electric field: the occurrence of a resonance frequency. Z Naturforsch C Biosci. 1981 Jan-Feb;36(1-2):173-7. doi: 10.1515/znc-1981-1-229.

  PMID: 7010816 BACKGROUND

• Holzapfel C, Vienken J, Zimmermann U. Rotation of cells in an alternating electric field: theory and experimental proof. J Membr Biol. 1982;67(1):13-26. doi: 10.1007/BF01868644.

  PMID: 7097755 BACKGROUND

• Pawlowski P, Szutowicz I, Marszalek P, Fikus M. Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field. Biophys J. 1993 Jul;65(1):541-9. doi: 10.1016/S0006-3495(93)81056-7.

  PMID: 8369458 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

• Zhao M, Forrester JV, McCaig CD. A small, physiological electric field orients cell division. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4942-6. doi: 10.1073/pnas.96.9.4942.

  PMID: 10220398 BACKGROUND

• Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102 ( Pt 3):401-16. doi: 10.1242/jcs.102.3.401.

  PMID: 1506423 BACKGROUND

• Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. doi: 10.1056/NEJM199504133321507. No abstract available.

  PMID: 7885406 BACKGROUND

• Kline-Smith SL, Walczak CE. The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells. Mol Biol Cell. 2002 Aug;13(8):2718-31. doi: 10.1091/mbc.e01-12-0143.

  PMID: 12181341 BACKGROUND

• Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ. Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol. 2000 Sep 4;150(5):975-88. doi: 10.1083/jcb.150.5.975.

  PMID: 10973989 BACKGROUND

• Maiato H, Sampaio P, Lemos CL, Findlay J, Carmena M, Earnshaw WC, Sunkel CE. MAST/Orbit has a role in microtubule-kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity. J Cell Biol. 2002 May 27;157(5):749-60. doi: 10.1083/jcb.200201101. Epub 2002 May 28.

  PMID: 12034769 BACKGROUND

• Gagliardi LJ. Electrostatic force in prometaphase, metaphase, and anaphase-A chromosome motions. Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jul;66(1 Pt 1):011901. doi: 10.1103/PhysRevE.66.011901. Epub 2002 Jul 12.

  PMID: 12241378 BACKGROUND

• Fishkind DJ, Silverman JD, Wang YL. Function of spindle microtubules in directing cortical movement and actin filament organization in dividing cultured cells. J Cell Sci. 1996 Aug;109 ( Pt 8):2041-51. doi: 10.1242/jcs.109.8.2041.

  PMID: 8856500 BACKGROUND

• Dogterom M, Yurke B. Measurement of the force-velocity relation for growing microtubules. Science. 1997 Oct 31;278(5339):856-60. doi: 10.1126/science.278.5339.856.

  PMID: 9346483 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, Schneiderman RS, Dbaly V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys. 2009 Jan 8;9:1. doi: 10.1186/1756-6649-9-1.

  PMID: 19133110 BACKGROUND

• Stupp R, Wong E, Scott C et al. Interim analysis of the EF-14 trial: a prospective, multi-center trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM. Neuro Oncol 2014;16(suppl 5):v167.

  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, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.

  PMID: 23891283 BACKGROUND

• Giladi M, Zielinska-Chomej K, Tichon A et al. The effect of alternating electric fields (TTFields) on inhibition of repair of DNA damage induced by ionizing radiation and sensitization of glioma and non-small cell lung cancer cells to radiation. J Clin Oncol 2014;32(suppl;abstr e22239).

  BACKGROUND

• Zielinska-Chomej K, Grozman V, Tu J, Viktorsson K, Lewensohn R. Analysis of combination of tumor treating fields (TTFields) with radiotherapy in non-small cell lung cancer. Neuro Oncol 2013;15(suppl 3):ET-033.

  BACKGROUND

• Lacouture ME, Davis ME, Elzinga G, Butowski N, Tran D, Villano JL, DiMeglio L, Davies AM, Wong ET. Characterization and management of dermatologic adverse events with the NovoTTF-100A System, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma. Semin Oncol. 2014 Jun;41 Suppl 4:S1-14. doi: 10.1053/j.seminoncol.2014.03.011. Epub 2014 Mar 19.

  PMID: 24794308 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Samuel Goldlust, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, single arm, non-randomized, open label pilot

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 28, 2017
• Study Start: July 26, 2017
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)