Effect of TTFields (150kHz) in Non-small Cell Lung Cancer (NSCLC) Patients With 1-5 Brain Metastases Following Optimal Standard Local Treatment (COMET)

NCT01755624 | Unknown Phase 2

• 1 other identifier: EF-21
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 7

Brief Summary

The study is a prospective, randomly controlled phase II trial, designed to test the efficacy, safety and neurocognitive outcomes of a medical device, the NovoTTF-100A, in the treatment of NSCLC patients with controlled systemic disease, following optimal standard local treatment for 1-5 brain metastases (BM). The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Conditions

1-5 Brain Metastases From Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLC; Brain metastases; Treatment; Minimal toxicity; TTFields; TTF; Tumor Treating Fields; NovoCure

Outcome Measures

Primary Outcomes (1)

• Time to Local and Distant Progression in The Brain

  2 years

Secondary Outcomes (6)

• Overall Survival

  2 years

• 6-Month Disease Control Rate in The Brain

  2 years

• Neurocognitive Function (MMSE and HVLT)

  2 years

• Quality of life (QLQ-C30 and BN-20)

  2 years

• Overall (systemic) Progression-Free Survival (RECIST Criteria)

  2 years

Study Arms (2)

NovoTTF-100A device

EXPERIMENTAL

Patients will be treated continuously with the NovoTTF-100A device. NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.

Device: NovoTTF-100A device

Best Standard of Care

ACTIVE COMPARATOR

Patients will be treated as the best known standard of care for Non-Small Cell Lung Cancer metastatic to the brain.

Other: Best Standard of Care

Interventions

NovoTTF-100A device DEVICE

NovoTTF-100A device

Best Standard of Care OTHER

Best Standard of Care

Eligibility Criteria

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

You may qualify if:

• years of age and older
• Life expectancy of ≥ 3 months
• Performance status WHO 0-2 (may be assessed under steroid therapy)
• New diagnosis of BM from a histologically or cytologically confirmed primary or metastatic NSCLC tumor, meeting 1 of the following criteria:
• Stable systemic cancer for the last 3 months (achieved by surgery, radiotherapy, or chemotherapy), defined as absence of symptomatic and radiological progression, according to RECIST Criteria
• Asymptomatic synchronous primary tumor (treatable by surgery, radiotherapy, or chemotherapy)
• BM biopsy required if no extracranial tumor (unknown primary tumor) OR extracranial diagnosis made more than 4 years previously
• Must have one to five brain lesions, confirmed by contrast enhanced MRI, all amenable either surgical resection, or to SRS according to the following criteria:
• Largest diameter ≤ 3.5 cm for single metastasis
• Largest diameter ≤ 2.5 cm for 2 to 5 metastases
• Stable or decreasing dose of steroids for at least 5 days before screening
• Patients must be receiving optimal therapy for their extracranial disease according to local practice at each center. Patients may continue on systemic therapy while receiving TTField therapy

You may not qualify if:

• Infratentorial metastases
• Leptomeningeal metastases
• Patients who previously received WBRT or SRS for BM (prior resection is allowed as long as any remaining tumor is treated under the protocol)
• Significant co-morbidity which is expected to affect patient's prognosis or ability to receive optimal systemic therapy:
• Inadequate and clinically relevant hematological, hepatic and renal abnormalities defined as: Neutrophil count \> 1.5 x 10 9/L and platelet count \> 100 x 10 9/L; bilirubin \< 1.5 x ULN; AST and/or ALT \< 2.5 x ULN or \< 5 x ULN is patient has documented liver metastases; and serum creatinine \< 1.5 x ULN
• History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
• History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial
• History of cerebrovascular accident (CVA) within 6 months prior to randomization
• Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
• History of any psychiatric condition that might impair the patient's ability to understand or comply with the requirements of the study or to provide consent
• Pregnant, or women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception
• Unable to operate the NovoTTF-100A device independently or with the help of a caregiver
• Implantable electronic medical devices in the brain
• Known allergies to medical adhesives or hydrogel
• Concurrent brain directed therapy (beyond SRS, surgery and TTField therapy as per protocol)

Sponsors & Collaborators

• NovoCure Ltd.: lead

Study Sites (7)

Na Homolce Hospital

Prague, Czechia

Location

Hopital Neurologique Pierre Wertheimer

Lyon, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Ospedale Lecco

Lecco, Italy

Location

Medical University of Gdańsk

Gdansk, Poland

Location

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, Poland

Location

ICO L'Hospitalet - Hospital Duran i Reynals

Barcelona, Spain

Location

Related Publications (7)

• 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

• 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

• 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

• 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

• Weinberg, U., et al. An Open Label Pilot Study of Tumor Treating Fields (TTFields) in Combination with Pemetrexed for Advanced Non-small Cell Lung Cancer (NSCLC). in ERS Annual Congress. 2010. Publisher: Abstract 363.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Andrea Salamaggi, MD

  Lecco General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 24, 2012
• Study Start: January 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: September 21, 2016

Record last verified: 2016-07

Locations

ES (1); IT (1); CZ (1); FR (2); PL (2)