Official Title
LUNAR: Pivotal, Randomized, Open-label Study of Tumour Treating Fields (TTFields) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure
Summary:
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 tumour, by
means of surface, insulated electrode arrays.
Trial Description
Primary Outcome:
- Overall survival of patients treated with TTFields +
docetaxel or immune checkpoint inhibitors vs. docetaxel or immune checkpoint
inhibitors alone (superiority analysis)
Secondary Outcome:
- Overall survival of patients treated with TTFields +
docetaxel vs. docetaxel alone (superiority analysis)
- Overall survival of patients treated with TTFields + immune
checkpoint inhibitors vs. immune checkpoint inhibitors alone (superiority)
- Overall Survival of patients treated with TTFields +
docetaxel Vs. immune checkpoint inhibitors alone (non-inferiority analysis)
- Progression-free survival of patients treated with docetaxel
or immune checkpoint inhibitors + TTFields vs. docetaxel or immune checkpoint
inhibitors alone, based on RECIST Criteria
- 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.
- Quality of life using the EORTC QLQ C30 questionnaire with
LC13 addendum
- Analyses of the effects of NovoTTF-100L with each type of
immune checkpoint inhibitor on overall survival and progression free survival
- Analysis of the effects of NovoTTF-100L on overall survival
and progression free survival within each histological subgroup (squamous and
non-squamous)
- The effect of treatment compliance with NovoTTF-100L on
overall survival and progression free survival outcomes
- Adverse events, severity and frequency based on Common
Terminology Criteria for Adverse Events (CTCAE) V4.03
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 tumour
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 Tumours) (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 (Tumour 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, tumour 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 this trial on ClinicalTrials.gov
