1-5 Brain Metastases From Non-Small Cell Lung Cancer Clinical Trial
Official title:
A Phase II Randomized Study of TTField Therapy (150 kHz) Versus Supportive Care in Non-small Cell Lung Cancer Patients With 1-5 Brain Metastases Following Optimal Standard Local Treatment
The study is a prospective, randomly controlled phase II trial, designed to test the efficacy, safety and neurocognitive outcomes of a medical device, the NovoTTF-100A, in the treatment of NSCLC patients with controlled systemic disease, following optimal standard local treatment for 1-5 brain metastases (BM). 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.
PAST PRE CLINICAL AND CLINICAL EXPERIENCE:
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.
DESCRIPTION OF THE TRIAL:
All patients included in this trial are diagnosed with NSCLC, and have stable systemic
disease with 1-5 supratentorial brain metastases who are amenable to optimal standard local
treatment (surgical resection/stereotactic radio surgery (SRS)/both). 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.
On both arms, patients who recur in the brain will be offered one of the following salvage
treatments (according to local practice) including, but not limited to:
1. Surgery (or repeat surgery)
2. SRS (or repeat SRS)
3. Whole brain radiotherapy (WBRT)
Patients on Arm II may cross over to TTFields therapy after salvage therapy if investigators
believe it is in the best interest of the patients and patients agree.
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 a 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.
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 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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment