Clinical trial NCT02831959: Pivotal, Open-label, Randomized Study of Radiosurgery With or Without Tumor Treating Fields (TTFields) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC).
Official title: Pivotal, Open-label, Randomized Study of Radiosurgery With or Without Tumor Treating Fields (TTFields) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Metastases From Non-small Cell Lung Cancer (NSCLC)
Keywords: Non-Small Cell Lung Cancer
NSCLC
Brain metastases
Treatment
Minimal toxicity
TTFields
TTF
Tumor Treating Fields
Novocure
SRS
Stereotactic radiosurgery
Lead sponsor: NovoCure Ltd.
Sponsor class: INDUSTRY
First posted: 2016-07-13
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a prospective, randomized controlled phase III trial, to test the efficacy, safety and neurocognitive outcomes of advanced NSCLC patients, following stereotactic radiosurgery (SRS) for 1 inoperable brain metastasis or 2-10 brain metastases, treated with NovoTTF-200M and supportive treatment compared to supportive treatment alone. 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.

Detailed description: PAST PRE-CLINICAL AND CLINICAL EXPERIENCE:

The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.

In a pilot study, 42 patients with advanced NSCLC who had tumor progression after at least one line of prior chemotherapy, received pemetrexed together with TTFields (150 kHz) applied to the chest and upper abdomen until disease progression (Pless M., et al., Lung Cancer 2011). Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone.

In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life (Stupp R., et al., JAMA 2015).

Applying TTFields at 150 kHz to the brain for the treatment of 1-5 brain metastasis from NSCLC using the NovoTTF-100M device has been demonstrated to be safe in a pilot study, where patients were randomized after local therapy of their brain metastasis by neurosurgery and/or stereotactic radiosurgery to receive either NovoTTF-100M treatment or supportive care alone. Eighteen (18) patients have been enrolled in the study. There have been no device-related serious adverse events (SAE) reported to date (Brozova H., et al., Neuro Oncol 2016).

DESCRIPTION OF THE TRIAL:

All patients included in this trial are patients with 1-10 brain metastases from NSCLC which are amenable to stereotactic radiosurgery (SRS). In addition, all patients must meet all eligibility criteria.

Eligible patients will be randomly assigned to one of two groups:

1. Patients undergo SRS followed by TTFields using the NovoTTF-200M System
2. Patients undergo SRS alone and receive supportive care. Patients in both arms of the study may receive systemic therapy for their NSCLC at the discretion of their treating physician.

Patients will be randomized at a 1:1 ratio. Baseline tests will be performed in patients enrolled in both arms. If assigned to the NovoTTF-200M group, the patients will be treated continuously with the device until second intracranial progression.

On both arms, patients who recur anywhere in the brain will be offered one of the following salvage treatments (according to local practice) including, but not limited to:

* Surgery
* Repeat SRS
* Whole brain radiotherapy (WBRT) Patients on the control arm will be offered to cross over to the NovoTTF-200M arm of the study and receive TTFields with or without salvage therapy for second intracranial progression if the investigator believes it is in the best interest of the patient and patient agrees.

SCIENTIFIC BACKGROUND:

Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet.

Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (150 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating.

The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause electrically- charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death.. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors related to other cellular components since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, results in cellular death or reverses after continuous exposure to TTFields.

Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach. Finally, the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues. In conclusion, TTFields hold the promise of serving as a brand new treatment for brain metastases from NSCLC with very few side effects.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age and older
2. Life expectancy of ≥ 3 months
3. New diagnosis of brain metastases from a histologically or cytologically confirmed primary or metastatic NSCLC tumor within 5 years of registration on the study. If the original histological proof of malignancy is greater than 5 years, then pathological confirmation is required (i.e.: from extra-cranial or intracranial disease).

5. 1 inoperable brain metastasis or 2- 10 brain lesions per screening MRI, confirmed by contrast enhanced MRI amenable to SRS according to the following criteria:

a. largest tumor volume \< 10 cc b. longest tumor diameter \< 3 cm c. Cumulative volume of all tumors ≤ 15 cc 6. At least one measurable disease per study protocol 7. 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 TTFields.

8. Able to operate the NovoTTF-200M device independently or with the help of a caregiver 9. Clinical trials prior to enrollment are allowed, as long as no brain directed therapy was included (current treatment trials are exclusionary)

Exclusion Criteria:

1. Patients who are known to have somatic tumor mutations in the following genes, for which targeted agents are available that directly affect the treatment of brain metastasis: Anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), ROS-1 proto- oncogene, and proto-oncogene B-RAF
2. Patients who have a single, operable brain metastasis
3. Patients with significant edema leading to risk of brain herniation
4. Patients with midline shift \> 10mm
5. Patients with intractable seizures
6. Leptomeningeal metastases
7. Recurrent brain metastases
8. Prior WBRT for newly diagnosed brain metastases
9. Severe comorbidities:

   1. Clinically-significant inadequate hematological, hepatic and renal function, defined as: Neutrophil count \< 1.5 x 10 9/L and platelet count \< 100 x 10\^9/L; bilirubin \> 1.5 x upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) \> 2.5 x ULN or \> 5 x ULN if patient has documented liver metastases; and serum creatinine \> 1.5 x ULN
   2. 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).
   3. 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 study.
   4. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable
   5. Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
   6. 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
10. Implantable electronic medical devices in the brain
11. Known allergies to medical adhesives or hydrogel
12. Currently pregnant or breastfeeding
13. Planned concurrent brain directed therapy (beyond SRS and NovoTTF-200M as per protocol)

Primary outcomes:
measure: Time to intracranial progression
timeFrame: 3 years
Secondary outcomes:
measure: Time to neurocognitive failure
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Radiological response in the brain following study treatments
timeFrame: 3 years
measure: Time to second intracranial progression
timeFrame: 3 years
measure: Time to intracranial progression, measured from the date of first SRS treatment to intracranial progression (per modified RECIST 1.1 Criteria) or neurological death, whichever occurs first.
timeFrame: 3 years
measure: Time to first and second intracranial progression evaluated in two cohorts of patients, 1-4 brain metastases and 5-10 brain metastases.
timeFrame: 3 years
measure: Rate of intracranial progression at 2, 4, 6, 8, 10, 12 months after first SRS treatment
timeFrame: 3 years
measure: Time to distant progression, as measured from the date of first SRS treatment to a new intracranial lesion
timeFrame: 3 years
measure: Rate of decline in cognitive function as measured by HVLT-R free recall, delayed recall and delayed recognition, COWAT and TMT Parts A and B at 2, 4, 6, 8, 10, 12 months follow-up.
timeFrame: 3 years
measure: Neurocognitive failure-free survival
timeFrame: 3 years
measure: Quality of Life using the EORTC QLQ C30 with BN20 addendum
timeFrame: 3 years
measure: Toxicity during NovoTTF-200M treatment based on incidence and severity of treatment emergent adverse events as evaluated using the CTCAE version 4.0
timeFrame: 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Birmingham
country: United States
facility: Grandview Medical Center - Cancer Center
state: Alabama
city: Mobile
country: United States
facility: Infirmary Cancer Care
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Long Beach
country: United States
facility: MemorialCare Cancer Institute
state: California
city: Orange
country: United States
facility: The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente Redwood City
state: California
city: Sacramento
country: United States
facility: Dignity Health - Mercy Cancer Centers
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Diego
country: United States
facility: Sharp HealthCare
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Grand Junction
country: United States
facility: St. Mary's Medical Center - Grand Junction
state: Colorado
city: Greeley
country: United States
facility: Banner North Colorado Medical Center (NCMC) - Oncology - Greeley
state: Colorado
city: Loveland
country: United States
facility: Banner MD Anderson Cancer Center - McKee Medical Center
state: Colorado
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Adult Oncology Research
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center INC
state: Florida
city: Atlanta
country: United States
facility: Piedmont Brain Tumor Center
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Warrenville
country: United States
facility: CDH-Delnor Health System
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky HealthCare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville-James Graham Brown Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Shreveport
country: United States
facility: Willis-Knighton Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital - Givens Brain Tumor Center
state: Minnesota
city: Minneapolis
country: United States
facility: John Nasseff Neuroscience Institute ANW Brain Tumor Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center (UMMC) - Fairview - Masonic Cancer Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center, University of Missouri Healthcare
state: Missouri
city: Saint Louis
country: United States
facility: Oncology Research | Mercy Research
state: Missouri
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Chapel Hill
country: United States
facility: UNC - Lineberger Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina- Hollings Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health - Upstate
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Baroness Hospital
state: Tennessee
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Mischer Neuroscience Associates - Texas Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: McKinney
country: United States
facility: Texas Oncology
state: Texas
city: Plano
country: United States
facility: Texas Oncology
state: Texas
city: Waco
country: United States
facility: Baylor Scott & White Medical Center - Temple
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski EAD, Department of Medical Oncology
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sofiamed, Department of Medical Oncology
city: Winnipeg
country: Canada
facility: Cancercare Manitoba
state: Manitoba
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Le CIUSSS de I'Est-de-L'ile de Montreal - Hôpital Maisonneuve Rosemont
state: Quebec
city: Sherbrooke
country: Canada
facility: (CHUS) Centre Hospitalier Universitaire de Sherbrooke, Service de Neurochirurgie
state: Quebec
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Chaoyang
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Zigong
country: China
facility: Zigong Fourth People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Xuhui District
city: Zhejiang
country: China
facility: Taizhou Hospital, Zhejiang Province
state: Zhejiang
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Hebei
country: China
facility: The Second Affiliated Hospital Of Xingtai Medical College
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shenzhen
country: China
facility: The University of Hong Kong-Shenzhen Hospital
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Sveta Nedelja
country: Croatia
facility: Radiochirugia Zagreb
city: Lille
country: France
facility: University Hospital Lille
city: Marseille
country: France
facility: Clairval Hospital Center
city: Paris
country: France
facility: Hopital Pitié-Salpétriere
city: Saint-Étienne
country: France
facility: Centre Hospitalier Universitaire de Saint-Étienne
city: Berlin
country: Germany
facility: Klinik für Radioonkologie und Strahlentherapie der Charité Universitätsmedizin Berlin Campus Charité Virchow-Klinikum
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Frankfurt am Main
country: Germany
facility: Dr. Senckenbergisches Institut for Neurooncology,
city: Frankfurt am main
country: Germany
facility: Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum der Neurologie und Neurochirurgie
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale), Klinik für Innere Medizin IV, Hämatologie / Onkologie
city: Heidelberg
country: Germany
facility: Heidelberg University Clinic for Radiooncology and Radiation Therapy
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Budapest
country: Hungary
facility: National Koranyi Institute of Tb and Pulmonology
city: Szekszárd
country: Hungary
facility: Onkologiai Osztaly, Balassa Janos Korhaz
city: Szolnok
country: Hungary
facility: Geza Hetenyi Hospital-Clinic of Jasz-Nagykun-Szolnok County
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Avellino
country: Italy
facility: A.O.S.G. Moscati Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità
city: Bergamo
country: Italy
facility: General Hospital Gavazzeni
city: Firenze
country: Italy
facility: Radioterapia Oncologica AOU Careggi
city: Lecco
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Lecco
city: Messina
country: Italy
facility: University Hospital of Messina AOU Policlinico "G. Martino"
city: Milan
country: Italy
facility: The IRCCS Carlo Besta Neurological Institute Foundation
city: Torino
country: Italy
facility: A.O.U Città della Salute e della Scienza di Torino
city: Bydgoszcz
country: Poland
facility: Marek Harat Private Practice, Neurosurgery and Radiation Oncology
city: Gdańsk
country: Poland
facility: University Clinical Center
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie National Research Institute of Oncology
city: Lublin
country: Poland
facility: MS Clinsearch Sp. z.o.o.
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
city: Warsaw
country: Poland
facility: Gamma Knife Center Warsaw
city: Belgrad
country: Serbia
facility: Center for Neuro-oncology, Neurosurgery Clinic, Clinical Center of Serbia
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro Edificio CIOCC
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Miami Cancer Institute, Miami FL USA
name: Minesh Mehta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Anderson Cancer Center, Houston TX USA
name: Paul Brown, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern Medicine Cancer Center, Warenville IL USA
name: Vinai Gondi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic, Cleveland OH USA
name: Manmeet Ahluwalia, MD
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
citation: Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, Bendszus M, Brown PD, Camidge DR, Chang SM, Dancey J, de Vries EG, Gaspar LE, Harris GJ, Hodi FS, Kalkanis SN, Linskey ME, Macdonald DR, Margolin K, Mehta MP, Schiff D, Soffietti R, Suh JH, van den Bent MJ, Vogelbaum MA, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015 Jun;16(6):e270-8. doi: 10.1016/S1470-2045(15)70057-4. Epub 2015 May 27.
citation: Brozova H, Lucas A, Salmaggi A, Vymazal J. COMET: A phase II randomized study of TTFields versus supportive care in non-small cell lung cancer patients with 1-5 brain metastases - initial safety results. Neuro Oncol. 2015 Nov; 17 (suppl 5): v46. doi:10.1093/neuonc/nov208.6