Lung Cancer Clinical Trial

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)

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.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

22 years of age and older (some regional variations to inclusion age exist)
Life expectancy of ≥ 3 months
Histological diagnosis of squamous or non-squamous, inoperable, metastatic NSCLC

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

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.
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.
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.
ECOG Score of 0-2
Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimen
Able to operate the NovoTTF-200T device independently or with the help of a caregiver
Signed informed consent for the study protocol

Exclusion Criteria:

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:

The patients are neurologically returned to baseline (except for residual signs or symptoms related to CNS treatment).
No treatment for the metastases to CNS during the screening period (e.g. surgery, radiotherapy, corticosteroid therapy- prednisone > 10 mg/day or equivalent).
No progress in CNS lesions as indicated by MRI within 14 days prior to randomization.
No meningeal metastasis or spinal cord compression.
Patients planned to receive immune checkpoint inhibitor with contra-indications to receive immunotherapy
Patients planned to receive docetaxel with contra-indications to receive docetaxel

Severe comorbidities:

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
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 pericarditis
History of interstitial lung disease
History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable
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 patient's ability to understand or comply with the requirements of the study or to provide consent
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
Concurrent treatment with other experimental treatments for NSCLC while on the study
Implantable electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso
Known allergies to medical adhesives or hydrogel
Pregnancy or breast-feeding (patients with reproductive potential must use effective contraception methods throughout the entire study period, as determined by their investigator/gynecologist)
Admitted to an institution by administrative or court order

Study is for people with:

Lung Cancer

Phase:

Phase 3

Estimated Enrollment:

276

Study ID:

NCT02973789

Recruitment Status:

Active, not recruiting

Sponsor:

NovoCure GmbH

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There are 93 Locations for this study

See Locations Near You

Central Alabama Research
Birmingham Alabama, 35209, United States
Ironwood Cancer & Research Center
Chandler Arizona, 85224, United States
Cancer Center at St. Joseph Hospital and Medical Center
Phoenix Arizona, 85004, United States
Beverly Hills Cancer Center
Beverly Hills California, 90211, United States
California Cancer Associates for Research and Excellence, Inc. cCARE
Fresno California, 93720, United States
St. Joseph Heritage Healthcare
Fullerton California, 92835, United States
Saddleback Memorial Medical Center
Laguna Hills California, 92653, United States
Redlands Community Hospital (Emad Ibrahim, MD, Inc.)
Redlands California, 92373, United States
Dignity Health - Mercy Cancer Centers
Sacramento California, 95186, United States
Sutter Institute for Medical Research
Sacramento California, 95816, United States
Innovative Clinical Research Institute
Whittier California, 90603, United States
Banner MD Anderson Cancer Center at North Colorado Medical Center
Greeley Colorado, 80631, United States
Associated Neurologists of Southern CT, P.C.
Fairfield Connecticut, 06824, United States
Washington Cancer Institute at MedStar Washington Hospital Center
Washington District of Columbia, 20010, United States
GenesisCare USA
Jacksonville Florida, 32204, United States
Mount Sinai Medical Center
Miami Beach Florida, 33140, United States
Miami Cancer Institute
Miami Florida, 33176, United States
AdventHealth Orlando
Orlando Florida, 32804, United States
Adult Oncology Research
Orlando Florida, 32806, United States
BRCR Medical Center INC
Plantation Florida, , United States
University of Illinois Cancer Center
Chicago Illinois, 60612, United States
Illinois CancerCare, P.C.
Peoria Illinois, 61615, United States
Southern Illinois University, School of Medicine, Simmons Cancer Institute at SIU
Springfield Illinois, 62702, United States
Franciscan Health Indianapolis
Indianapolis Indiana, 46237, United States
University of Kansas Cancer Center
Westwood Kansas, 66205, United States
Norton Cancer Institute
Louisville Kentucky, 40202, United States
University Medical Center, Inc; DBA University of Louisville
Louisville Kentucky, 40202, United States
LSU Health Sciences Center -New Orleans
New Orleans Louisiana, 70112, United States
Tulane Cancer Center
New Orleans Louisiana, 70112, United States
CHRISTUS Health
Shreveport Louisiana, 71105, United States
Central Maine Medical Center
Lewiston Maine, , United States
University of Maryland School of Medicine
Baltimore Maryland, 21201, United States
Tufts Medical Center, Division of Hematology and Oncology
Boston Massachusetts, 02111, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Clinical Oncology Associates
Farmington Hills Michigan, 48336, United States
Detroit Clinical Research Center
Farmington Hills Michigan, 48336, United States
Saint Joseph Mercy Health System
Ypsilanti Michigan, 48197, United States
HealthPartners Institute, Regions Cancer Care Center
Saint Paul Minnesota, 55101, United States
Saint Luke's Cancer Institute
Kansas City Missouri, 64111, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
CHI Health Research Center
Omaha Nebraska, 68124, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha Nebraska, 68130, United States
University of Nebraska Medical Center
Omaha Nebraska, , United States
OptumCare Cancer Care
Las Vegas Nevada, 89102, United States
Renown Regional Medical Center Institute for Cancer
Reno Nevada, 89502, United States
Presbyterian Cancer Center
Albuquerque New Mexico, 87110, United States
New York-Presbyterian/Queens Radiation Oncology
Flushing New York, 11355, United States
Northern Westchester Hospital
Mount Kisco New York, 10549, United States
Stony Brook Cancer Center
Stony Brook New York, 11794, United States
Oncology Specialists of Charlotte
Charlotte North Carolina, 28204, United States
W.G. Bill Hefner VA Med Center
Salisbury North Carolina, 28144, United States
Piedmont Radiation Oncology, PA
Winston-Salem North Carolina, 27103, United States
Summa Health
Akron Ohio, 44304, United States
Toledo Clinic Cancer Center
Toledo Ohio, 43623, United States
Vita Medical Associates, P.C.
Bethlehem Pennsylvania, 18015, United States
Geisinger Cancer Institute
Danville Pennsylvania, 17822, United States
UT/Erlanger Oncology & Hematology
Chattanooga Tennessee, 37403, United States
Texas Oncology - Amarillo
Amarillo Texas, 79106, United States
Texas Oncology - Arlington
Arlington Texas, 76012, United States
Christus Health Spohn Ministry
Corpus Christi Texas, 78404, United States
Dallas VA Medical Center
Dallas Texas, 75216, United States
Texas Oncology- Baylor Charles A. Sammons Cancer Center
Dallas Texas, 75246, United States
The University of Texas Southwestern Medical Center
Dallas Texas, 75390, United States
Oncology Consultants, P.A.
Houston Texas, 77030, United States
Texas Oncology-McKinney
McKinney Texas, 75071, United States
Texas Oncology - Paris
Paris Texas, 75460, United States
Texas Oncology- Plano West
Plano Texas, 75093, United States
Baylor Scott & White Health/McClinton Cancer Center
Waco Texas, 76712, United States
Texas Oncology-Waco
Waco Texas, 76712, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City Utah, 84112, United States
Overlake Medical Center & Clinics
Bellevue Washington, 98004, United States
UW Carbone Cancer Center
Madison Wisconsin, 53792, United States
Medical University Salzburg, State Hospital, University hospital for internal medicine III / PMU
Salzburg , 5020, Austria
Institut Jules Bordet - Department of Intensive Care and Thoracic Oncology
Brussels , 1000, Belgium
Clinique André Renard Herstal Oncologie
Herstal , 4040, Belgium
AZ Sint Maarten
Mechelen , 2800, Belgium
Complex Oncology Center (COC) - Plovdiv EOOD,
Plovdiv , 4004, Bulgaria
McGill University Health Centre
Montréal Quebec, H4A 3, 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, J1H 5, Canada
Allan Blair Cancer Center
Regina Saskatchewan, S4T 7, Canada
Beijing Cancer Hospital
Beijing Beijing, , China
Affiliated Cancer Hospital of Guangzhou Medical University
Guangzhou Guangdong, , China
Henan Cancer Hospital
Zhengzhou Henan, 45000, China
Henan Provincial People's Hospital
Zhengzhou Henan, 45003, China
PKUCare Luzhong Hospital
Zibo Shandong, 25001, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou Zhejiang, 31000, China
Zhejiang Cancer Hospital
Hangzhou Zhejiang, 31100, China
Sun Yat-sen University Cancer Center
Guangzhou , , China
University Hospital Centre Zagreb
Zagreb , 10000, Croatia
General University Hospital in Prague
Prague , , Czechia
Thomayerova Nemocnice Dept. of Pneumology
Prague , , Czechia
Vitkovicka nemocnice
Vitkovice , , Czechia
Centre Hospitalier de Beauvais
Beauvais , 60021, France
INSTITUT BERGONIE Centre Régional de Lutte Contre le Cancer
Bordeaux , , France
Groupe Hospitalier Bretagne Sud
Lorient , 56100, France
CHU Caremeau Service de Pneumologie
Nîmes , 30029, France
AH-HP Hôpital Saint Louis
Paris , , France
Centre Hospitalier de Saint-Quentin Service de pneumologie
Saint-Quentin , 21000, France
Universitätsklinikum Halle - Universitätsklinik und Poliklinik für Innere Medizin IV
Halle (Saale) , , Germany
Queen Mary Hospital
Hong Kong , , Hong Kong
Tolna County, Balassa Janos Hospital, Department of oncology
Szekszárd , 7100, Hungary
ASL 3, Ospedale Villa Scassi
Genova , 16132, 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 , 21047, Italy
St Jansdal Ziekenhuis
Harderwijk , , Netherlands
Erasmus Mc
Rotterdam , 3015, Netherlands
Uniwersyteckie Centrum Kliniczne
Gdansk , , Poland
MS Clinsearch Specjalistyczny NZOZ
Lublin , , Poland
Clinical Hospital of Przemienienia Pańskiego UM in Poznaniu
Poznan , , Poland
Samodzielny Publiczny Wojewódzki Szpital Zespolony w Szczecinie
Szczecin , 70-89, Poland
Centrum Terapii Współczesnej
Łódź , , Poland
Bezanijska kosa Clinical Hospital Center
Belgrade , 11080, Serbia
University Clinical Center Kragujevac
Kragujevac , 34000, Serbia
Hospital Universitario Arnau de Vilanova
Lleida Catalonia, , Spain
Hospital Quirón Teknon, Instituto Oncológico Dr. Rosell
Barcelona , , 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 , 45071, Spain
Hospital Universitari i Politécnic La Fe
Valencia , , Spain
Kantonsspital Winterthur Tumorzentrum Winterthur
Winterthur , 8400, Switzerland

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 3

Estimated Enrollment:

276

Study ID:

NCT02973789

Recruitment Status:

Active, not recruiting

Sponsor:


NovoCure GmbH

How clear is this clinincal trial information?

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