Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM) - Full Text View

Sponsor:	NovoCure Ltd.
Information provided by:	NovoCure Ltd.
ClinicalTrials.gov Identifier:	NCT00916409

Purpose

The study is a prospective, randomly controlled pivotal trial, designed to test the efficacy and safety of a medical device, the NovoTTF-100A, as an adjuvant to the best standard of care in the treatment of newly diagnosed GBM patients. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields) to the region of the malignant tumor, by means of surface, insulated electrodes.

Condition	Intervention	Phase
Glioblastoma Multiforme	Device: NovoTTF-100A device Drug: Temozolomide	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	A Prospective, Multi-center Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients With Newly Diagnosed GBM.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by NovoCure Ltd.:

Primary Outcome Measures:

Progression Free Survival (PFS) time [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (OS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Progression free survival at 6 months (PFS6) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
1% and 2-year survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Radiological response (Macdonald criteria) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Quality of life assessment (EORTC QLQ-C30) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Adverse events severity and frequency [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	283
Study Start Date:	June 2009
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
NovoTTF-100A device in combination with Temozolomide: Experimental patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrodes on the head. The treatment enables the patient to maintain regular daily routine.	Device: NovoTTF-100A device patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrodes on the head. The treatment enables the patient to maintain regular daily routine.
Temozolomide alone, as the best known standard of care: Active Comparator Patients will be treated with Temozolomide, as the best known standard of care for Glioblastoma Multiforme patients.	Drug: Temozolomide maintenance Temozolomide will be administered according to the approved dosing scheme as follows: Maintenance Phase Cycle 1: Four weeks after completing the Temozolomide + Radiotherapy phase, Temozolomide is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment. Cycles 2-6: At the start of Cycle 2, the dose is escalated 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. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.

Arms

Assigned Interventions

NovoTTF-100A device in combination with Temozolomide: Experimental

patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrodes on the head. The treatment enables the patient to maintain regular daily routine.

Device: NovoTTF-100A device

patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrodes on the head. The treatment enables the patient to maintain regular daily routine.

Temozolomide alone, as the best known standard of care: Active Comparator

Patients will be treated with Temozolomide, as the best known standard of care for Glioblastoma Multiforme patients.

Drug: Temozolomide

maintenance Temozolomide will be administered according to the approved dosing scheme as follows: Maintenance Phase Cycle 1: Four weeks after completing the Temozolomide + Radiotherapy phase, Temozolomide is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment.

Cycles 2-6: At the start of Cycle 2, the dose is escalated 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. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pathological evidence of GBM using WHO classification criteria
> 18 years of age
Received maximal debulking surgery and radiotherapy with Temozolomide
Karnofsky scale ≥ 70
Life expectancy at least 3 months
Participants of childbearing age must use effective contraception
All patients must sign written informed consent
Treatment start date at least 4 weeks out from surgery
Treatment start date at least 4 weeks out but not more than 7 weeks from last dose of adjuvant Temozolomide
Treatment start date at least 4 weeks out from radiation therapy

Exclusion Criteria:

Progressive disease (according to MacDonald Criteria)
Actively participating in another clinical treatment trial
Pregnant
Significant co-morbidities at baseline which would prevent maintenance temozolomide treatment:
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 > upper limit of normal
6. Significant renal impairment (serum creatinine > 1.7 mg/dL)
Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias
Infra-tentorial tumor
Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to DTIC

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00916409

Contacts

Contact: Mike Ambrogi

mike@novo-cure.com

Show 22 Study Locations

Sponsors and Collaborators

NovoCure Ltd.

Investigators

Study Director:	Roger Stupp, MD	University of Lausanne Hospital - Multidisciplinary Oncology Center
Study Director:	Philip H. Gutin, MD	Memorial Sloan-Kettering Cancer Center
Study Director:	Eric T. Wong, MD	Beth Israel Deaconess Medical Center
Study Director:	Herbert H. Engelhard, MD, PhD	University of Illinois
Study Director:	Manfred Westphal, Prof. MD	Universitätsklinikum Hamburg-Eppendorf
Study Director:	Robert J. Weil, MD	The Cleveland Clinic

More Information

Publications:

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.

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. Epub 2007 Jun 5.

Salzberg M, Kirson E, Palti Y, Rochlitz C. A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. Onkologie. 2008 Jul;31(7):362-5. Epub 2008 Jun 24.

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 Apr 23; [Epub ahead of print]

Kirson ED, Schneiderman RS, Dbalý 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.

Responsible Party:	NovoCure Ltd. ( Mike Ambrogi )
Study ID Numbers:	EF-14
Study First Received:	June 5, 2009
Last Updated:	January 21, 2010
ClinicalTrials.gov Identifier:	NCT00916409 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by NovoCure Ltd.:

Glioblastoma Multiforme
Glioblastoma
GBM
Brain tumor
Treatment

Minimal toxicity
Newly Diagnosed
TTFields
Tumor Treating Fields
NovoCure

Additional relevant MeSH terms:

Glioblastoma
Neoplasms by Histologic Type
Dacarbazine
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Neoplasms, Nerve Tissue
Temozolomide
Pharmacologic Actions

Neuroectodermal Tumors
Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Glioma
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010