Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure (LUNAR)

NSCLC Clinical Trial

Official title:

LUNAR: Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02973789
• Other study ID #: EF-24
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: September 2023

Study information

• Verified date: September 2023
• Source: NovoCure Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-200T device, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum based treatment. 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.

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 and PD-1 inhibitors. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with PD-1 inhibitors. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment. In a pilot study, 42 patients with advanced NSCLC who had 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). The combination was well tolerated and the only device-related adverse event was mild to moderate contact dermatitis. 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). DESCRIPTION OF THE TRIAL: All patients included in this trial are patients with squamous or non-squamous, stage 4 NSCLC who had disease progression on or after receiving platinum based chemotherapy. In addition, all patients must meet all eligibility criteria. Eligible patients will be randomly assigned to one of two groups: Patients receive docetaxel or immune checkpoint inhibitor in combination with TTFields using the NovoTTF-100L System. Patients receive docetaxel or immune checkpoint inhibitor without TTFields. 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-100L group, the patients will be treated continuously with the device until disease progression in the thorax and/or liver according to RECIST or irRECIST (Immune-Related Response Evaluation Criteria In Solid Tumors) (depending if the patient is receiving docetaxel or immune checkpoint inhibitor, respectively). On both arms, patients who have disease progression according to RECIST or irRECIST (depending if the patient is receiving docetaxel or immune checkpoint inhibitor, respectively) will switch to a third line treatment according to local practice. 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 NSCLC with very few side effects.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 276
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

Inclusion Criteria:

1. 22 years of age and older (some regional variations to inclusion age exist)

2. Life expectancy of = 3 months

3. Histological diagnosis of squamous or non-squamous, inoperable, metastatic NSCLC

4. Diagnosis of radiological progression while on or after first platinum-based systemic therapy administered for advanced or metastatic disease.

1. Patients who received adjuvant or neoadjuvant platinum-based chemotherapy (after surgery and/or radiation therapy) and developed metastatic disease within 6 months of completing therapy are eligible.

2. Patients with metastatic disease more than 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum- based regimen given to treat the advanced or metastatic disease, are eligible.

3. Patients should not receive any systemic therapy after platinum failure before enrollment into the study. Maintenance therapy after platinum based therapy and prior to progression is allowed.

5. ECOG Score of 0-2

6. Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimen

7. Able to operate the NovoTTF-200T device independently or with the help of a caregiver

8. Signed informed consent for the study protocol

Exclusion Criteria:

1. Metastases to central nervous system (CNS) with clinical symptoms or evidence of new metastases to CNS during screening. Patients who previously received treatments for the metastases to CNS, are stable and meet the following requirements are allowed to

be enrolled:

1. The patients are neurologically returned to baseline (except for residual signs or symptoms related to CNS treatment).

2. No treatment for the metastases to CNS during the screening period (e.g. surgery, radiotherapy, corticosteroid therapy- prednisone > 10 mg/day or equivalent).

3. No progress in CNS lesions as indicated by MRI within 14 days prior to randomization.

4. No meningeal metastasis or spinal cord compression.

2. Patients planned to receive immune checkpoint inhibitor with contra-indications to receive immunotherapy

3. Patients planned to receive docetaxel with contra-indications to receive docetaxel

4. Severe comorbidities:

1. Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, 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 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 trial

4. History of pericarditis

5. History of interstitial lung disease

6. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable

7. Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy

8. 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

9. Any other malignancy requiring anti-tumor treatment in the past three years, excluding treated stage I prostate cancer, in situ cervical cancer, in situ breast cancer and non-melanomatous skin cancer

5. Concurrent treatment with other experimental treatments for NSCLC while on the study

6. Implantable electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso

7. Known allergies to medical adhesives or hydrogel

8. Pregnancy or breast-feeding (patients with reproductive potential must use effective contraception methods throughout the entire study period, as determined by their investigator/gynecologist)

9. Admitted to an institution by administrative or court order

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Nonsmall Cell Lung Cancer
• NSCLC

Intervention

Device:
• NovoTTF-200T
Patients receive continuous TTFields treatment using the NovoTTF-200T device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the chest. The treatment enables the patient to maintain regular daily routine. Other Name: TTFields Drug: Immune checkpoint inhibitors or docetaxel Patients receive standard of care with Immune checkpoint inhibitors or docetaxel

Drug:
• Immune checkpoint inhibitors or docetaxel
Patients receive standard of care with Immune checkpoint inhibitors or docetaxel

Locations

Country	Name	City	State
Austria	Medical University Salzburg, State Hospital, University hospital for internal medicine III / PMU	Salzburg
Belgium	Institut Jules Bordet - Department of Intensive Care and Thoracic Oncology	Brussels
Belgium	Clinique André Renard Herstal Oncologie	Herstal
Belgium	AZ Sint Maarten	Mechelen
Bulgaria	Complex Oncology Center (COC) - Plovdiv EOOD,	Plovdiv
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Allan Blair Cancer Center	Regina	Saskatchewan
Canada	Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS)	Sherbrooke	Quebec
China	Beijing Cancer Hospital	Beijing	Beijing
China	Affiliated Cancer Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	PKUCare Luzhong Hospital	Zibo	Shandong
Croatia	University Hospital Centre Zagreb	Zagreb
Czechia	General University Hospital in Prague	Prague
Czechia	Thomayerova Nemocnice Dept. of Pneumology	Prague
Czechia	Vitkovicka nemocnice	Vitkovice
France	Centre Hospitalier de Beauvais	Beauvais
France	INSTITUT BERGONIE Centre Régional de Lutte Contre le Cancer	Bordeaux
France	Groupe Hospitalier Bretagne Sud	Lorient
France	CHU Caremeau Service de Pneumologie	Nîmes
France	AH-HP Hôpital Saint Louis	Paris
France	Centre Hospitalier de Saint-Quentin Service de pneumologie	Saint-Quentin
Germany	Universitätsklinikum Halle - Universitätsklinik und Poliklinik für Innere Medizin IV	Halle (Saale)
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Tolna County, Balassa Janos Hospital, Department of oncology	Szekszárd
Italy	ASL 3, Ospedale Villa Scassi	Genova
Italy	IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola
Italy	UOC Oncologia Medica Presidio Ospedaliero di Ravenna AUSL della Romagna	Ravenna
Italy	Saronno Hospital	Saronno
Netherlands	St Jansdal Ziekenhuis	Harderwijk
Netherlands	Erasmus Mc	Rotterdam
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Terapii Wspólczesnej	Lódz
Poland	MS Clinsearch Specjalistyczny NZOZ	Lublin
Poland	Clinical Hospital of Przemienienia Panskiego UM in Poznaniu	Poznan
Poland	Samodzielny Publiczny Wojewódzki Szpital Zespolony w Szczecinie	Szczecin
Serbia	Bezanijska kosa Clinical Hospital Center	Belgrade
Serbia	University Clinical Center Kragujevac	Kragujevac
Spain	Hospital Quirón Teknon, Instituto Oncológico Dr. Rosell	Barcelona
Spain	Hospital Universitario Arnau de Vilanova	Lleida	Catalonia
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Regional Universitario Carlos Haya Medical Oncology Department	Málaga
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Universitari i Politécnic La Fe	Valencia
Switzerland	Kantonsspital Winterthur Tumorzentrum Winterthur	Winterthur
United States	Summa Health	Akron	Ohio
United States	Presbyterian Cancer Center	Albuquerque	New Mexico
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	Texas Oncology - Arlington	Arlington	Texas
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Overlake Medical Center & Clinics	Bellevue	Washington
United States	Vita Medical Associates, P.C.	Bethlehem	Pennsylvania
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Central Alabama Research	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Medical Center, Division of Hematology and Oncology	Boston	Massachusetts
United States	Ironwood Cancer & Research Center	Chandler	Arizona
United States	Oncology Specialists of Charlotte	Charlotte	North Carolina
United States	UT/Erlanger Oncology & Hematology	Chattanooga	Tennessee
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Christus Health Spohn Ministry	Corpus Christi	Texas
United States	Dallas VA Medical Center	Dallas	Texas
United States	Texas Oncology- Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Geisinger Cancer Institute	Danville	Pennsylvania
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Associated Neurologists of Southern CT, P.C.	Fairfield	Connecticut
United States	Clinical Oncology Associates	Farmington Hills	Michigan
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	New York-Presbyterian/Queens Radiation Oncology	Flushing	New York
United States	California Cancer Associates for Research and Excellence, Inc. cCARE	Fresno	California
United States	St. Joseph Heritage Healthcare	Fullerton	California
United States	Banner MD Anderson Cancer Center at North Colorado Medical Center	Greeley	Colorado
United States	Oncology Consultants, P.A.	Houston	Texas
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	GenesisCare USA	Jacksonville	Florida
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Saddleback Memorial Medical Center	Laguna Hills	California
United States	OptumCare Cancer Care	Las Vegas	Nevada
United States	Central Maine Medical Center	Lewiston	Maine
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University Medical Center, Inc; DBA University of Louisville	Louisville	Kentucky
United States	UW Carbone Cancer Center	Madison	Wisconsin
United States	Texas Oncology-McKinney	McKinney	Texas
United States	Miami Cancer Institute	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	LSU Health Sciences Center -New Orleans	New Orleans	Louisiana
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	CHI Health Research Center	Omaha	Nebraska
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Adult Oncology Research	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Texas Oncology - Paris	Paris	Texas
United States	Illinois CancerCare, P.C.	Peoria	Illinois
United States	Cancer Center at St. Joseph Hospital and Medical Center	Phoenix	Arizona
United States	Texas Oncology- Plano West	Plano	Texas
United States	BRCR Medical Center INC	Plantation	Florida
United States	Redlands Community Hospital (Emad Ibrahim, MD, Inc.)	Redlands	California
United States	Renown Regional Medical Center Institute for Cancer	Reno	Nevada
United States	Dignity Health - Mercy Cancer Centers	Sacramento	California
United States	Sutter Institute for Medical Research	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	HealthPartners Institute, Regions Cancer Care Center	Saint Paul	Minnesota
United States	W.G. Bill Hefner VA Med Center	Salisbury	North Carolina
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	CHRISTUS Health	Shreveport	Louisiana
United States	Southern Illinois University, School of Medicine, Simmons Cancer Institute at SIU	Springfield	Illinois
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Baylor Scott & White Health/McClinton Cancer Center	Waco	Texas
United States	Texas Oncology-Waco	Waco	Texas
United States	Washington Cancer Institute at MedStar Washington Hospital Center	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Innovative Clinical Research Institute	Whittier	California
United States	Piedmont Radiation Oncology, PA	Winston-Salem	North Carolina
United States	Saint Joseph Mercy Health System	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
NovoCure GmbH

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  China,  Croatia,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Netherlands,  Poland,  Serbia,  Spain,  Switzerland, 

References & Publications (9)

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. — View Citation

Giladi M, Weinberg U, Schneiderman RS, Porat Y, Munster M, Voloshin T, Blatt R, Cahal S, Itzhaki A, Onn A, Kirson ED, Palti Y. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo. Semin Oncol. 2014 Oct;41 Suppl 6:S35-41. doi: 10.1053/j.seminoncol.2014.09.006. Epub 2014 Sep 8. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669. — View Citation

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. — View Citation

Voloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, Palti Y. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy. Cancer Immunol Immunother. 2020 Jul;69(7):1191-1204. doi: 10.1007/s00262-020-02534-7. Epub 2020 Mar 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival of patients treated with TTFields + docetaxel or immune checkpoint inhibitors vs. docetaxel or immune checkpoint inhibitors alone (superiority analysis)		4 years
Secondary	Overall survival of patients treated with TTFields + docetaxel vs. docetaxel alone (superiority analysis)		4 years
Secondary	Overall survival of patients treated with TTFields + immune checkpoint inhibitors vs. immune checkpoint inhibitors alone (superiority)		4 years
Secondary	Overall Survival of patients treated with TTFields + docetaxel Vs. immune checkpoint inhibitors alone (non-inferiority analysis)		4 years
Secondary	Progression-free survival of patients treated with docetaxel or immune checkpoint inhibitors + TTFields vs. docetaxel or immune checkpoint inhibitors alone, based on RECIST Criteria		4 years
Secondary	Overall radiological response rate (based on RECIST criteria) of patients treated with docetaxel or Immune checkpoint inhibitors + TTFields vs. docetaxel or immune checkpoint inhibitors alone.		4 years
Secondary	Quality of life using the EORTC QLQ C30 questionnaire with LC13 addendum		4 years
Secondary	Analyses of the effects of NovoTTF-200T with each type of immune checkpoint inhibitor on overall survival and progression free survival		4 years
Secondary	Analysis of the effects of NovoTTF-200T on overall survival and progression free survival within each histological subgroup (squamous and non-squamous)		4 years
Secondary	The effect of treatment compliance with NovoTTF-200T on overall survival and progression free survival outcomes		4 years
Secondary	Adverse events, severity and frequency based on Common Terminology Criteria for Adverse Events (CTCAE) V4.03		4 years