Purpose

The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-100L System, 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.

Condition

Eligibility

Eligible Ages
Over 22 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. 22 years of age and older
  2. Life expectancy of ≥ 3 months
  3. Histological diagnosis of squamous or non-squamous, inoperable, stage 4 NSCLC
  4. Diagnosis of radiological progression while on or after first platinum-based systemic therapy
  5. Randomization within 28 days of diagnosis of last progression
  6. ECOG Score of 0-2
  7. Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimens
  8. Able to operate the NovoTTF-100L device independently or with the help of a caregiver
  9. Signed informed consent for the study protocol

Exclusion Criteria

  1. Presence of brain metastasis or leptomeningeal spread of the disease
  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:
  5. 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
  6. 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)
  7. 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
  8. History of pericarditis
  9. History of interstitial lung disease
  10. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable
  11. Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
  12. 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
  13. 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
  14. Concurrent treatment with other experimental treatments for NSCLC while on the study
  15. Implantable electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso
  16. Known allergies to medical adhesives or hydrogel
  17. Pregnancy or breast-feeding (patients with reproductive potential must use effective contraception methods throughout the entire study period, as determined by their investigator/gynecologist)
  18. Admitted to an institution by administrative or court order

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NovoTTF-100L
Patients receive TTFields using the NovoTTF-100L System together with immune checkpoint inhibitors or docetaxel
  • Device: NovoTTF-100L
    Patients receive continuous TTFields treatment using the NovoTTF-100L 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 names:
    • TTFields
  • Drug: Immune checkpoint inhibitors or docetaxel
    Patients receive standard of care with Immune checkpoint inhibitors or docetaxel
Active Comparator
Best Standard of Care
Patients receive best 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

Recruiting Locations

Washington Cancer Institute at MedStar Washington Hospital Center
Washington, District of Columbia 20010
Contact:
Edwards Okobi
202-877-3061
Okelue.e.okobi@medstar.net

More Details

NCT ID
NCT02973789
Status
Recruiting
Sponsor
NovoCure Ltd.

Study Contact

Antonia Mahnig
+41 41 455 36 32
clinicaltrials@novocure.com

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 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.