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A Phase II Randomized Study of TTField Therapy Versus Supportive Care in Non-small Cell Lung Cancer Patients With 1-3 Brain Metastases Following Stereotactic Radio-surgery

Phase 2
18 Years
Open (Enrolling)
1-3 Brain Metastases From Non-Small Cell Lung Cancer

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Trial Information

A Phase II Randomized Study of TTField Therapy Versus Supportive Care in Non-small Cell Lung Cancer Patients With 1-3 Brain Metastases Following Stereotactic Radio-surgery


The effect of the electric fields generated by the NovoTTF-100A device (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. TTField therapy has also
shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.

In a small scale pilot study, patients with stage IIIB- IV NSCLC who had had tumor
progression after at least one line of prior chemotherapy received Pemetrexed together with
TTField therapy applied to the chest and upper abdomen until disease progression. Efficacy
endpoints were remarkably high compared to historical data for Pemetrexed alone.

In a large prospective, randomized trial, in recurrent GBM. The outcome of subjects treated
with the NovoTTF-100A device was compared to those treated with an effective best standard
of care chemotherapy (including bevacizumab). NovoTTF-100A subjects had comparable overall
survival to subjects receiving the best available chemotherapy in the US today. Similar
results showing comparability of NovoTTF-100A to BSC chemotherapy were seen in all secondary
endpoints. Recurrent GBM patients treated with the NovoTTF-100A device in this trial
experienced fewer side effects in general, significantly fewer treatment related side
effects, and significantly lower gastrointestinal, hematological and infectious adverse
events compared to controls. The only device-related adverse events seen were a mild to
moderate skin irritation beneath the device electrodes. Finally, quality of life measures
were better in NovoTTF-100A subjects as a group when compared to subjects receiving
effective best standard of care chemotherapy.


All patients included in this trial are diagnosed with NSCLC, and have stable systemic
disease with 1-3 supratentorial brain metastases who are amenable to SRS. In addition, all
patients must meet all eligibility criteria.

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

1. Treatment with the NovoTTF-100A device together with best standard of care.

2. Best standard of care

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-100A group, the patients will be treated
continuously with the device until disease progression in the brain.

NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays
on the head. Electrode array placement will require shaving of the scalp before and
frequently during the treatment. After an initial short visit to the clinic for training and
monitoring, patients will be released to continue treatment at home where they can maintain
their regular daily routine.

During the trial, regardless of which treatment group the patient was assigned to, he or she
will need to return once every month to the clinic where an examination by a physician and a
routine laboratory examinations will be done. These routine visits will continue for as long
as the patient's disease is not progressing in the brain.

During the monthly follow up visits to the clinic patients will be examined physically and
neurologically. Additionally, routine blood tests will be performed. A routine MRI of the
head will be performed at baseline and every third month thereafter, until disease
progression in the brain. In addition neurocognitive test will be performed at baseline and
every third month thereafter, until disease progression in the brain. After this follow up
plan, patients will be contacted once per month by telephone to answer basic questions about
their health status.


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 the building blocks of these cells to move and pile up in such a
way that the cells physically explode. 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 cause these tiny motors to fall apart since they have a special type of
electric charge.

As a result of these two effects, cancer tumor growth is slowed and can even reverse 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.

In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very
few side effects and promising affectivity in slowing or reversing this disease.

Inclusion Criteria:

1. 18 years of age and older

2. Life expectancy of ≥ 3 months

3. Performance status WHO 0-2 (may be assessed under steroid therapy)

4. New diagnosis of BM from a histologically or cytologically confirmed primary or
metastatic NSCLC tumor, meeting 1 of the following criteria:

1. 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

2. Asymptomatic synchronous primary tumor (treatable by surgery, radiotherapy, or

5. BM biopsy required if no extracranial tumor (unknown primary tumor) OR extracranial
diagnosis made more than 4 years previously

6. Must have one to three brain lesions, confirmed by contrast enhanced MRI amenable to
SRS according to the following criteria:

1. Largest diameter ≤ 3.5 cm for single metastasis

2. Largest diameter ≤ 2.5 cm for 2 or 3 metastases

7. Stable or decreasing dose of steroids for at least 5 days before screening

8. 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

Exclusion Criteria:

1. Infratentorial metastases

2. Leptomeningeal metastases

3. Patients who previously received WBRT or SRS for BM

4. Significant co-morbidity which is expected to affect patient's prognosis or ability
to receive optimal systemic therapy:

1. 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

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 cerebrovascular accident (CVA) within 6 months prior to randomization

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 the patient's ability to
understand or comply with the requirements of the study or to provide consent

7. Pregnant, or women with an intact uterus (unless amenorrhoeic for the last 24
months) not using effective means of contraception

5. Unable to operate the NovoTTF-100A device independently or with the help of a

6. Implantable electronic medical devices in the brain

7. Known allergies to medical adhesives or hydrogel

8. Concurrent brain directed therapy (beyond SRS and TTField therapy as per protocol)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to Local and Distant Progression in The Brain

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Josef Vymazal, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Na Homolce, Prague


Israel: Ministry of Health

Study ID:




Start Date:

January 2013

Completion Date:

April 2015

Related Keywords:

  • 1-3 Brain Metastases From Non-Small Cell Lung Cancer
  • Non-Small Cell Lung Cancer
  • Brain metastases
  • Treatment
  • Minimal toxicity
  • TTFields
  • TTF
  • Tumor Treating Fields
  • NovoCure
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Brain Neoplasms