Official Title
Pivotal, Randomized, Open-label Study of Tumour Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-paclitaxel for Front-line Treatment of Locally-advanced Pancreatic Adenocarcinoma
Summary:
Brief Summary:
The study is a prospective, randomized controlled phase III trial aimed to test the efficacy
and safety of Tumour Treating Fields (TTFields) in combination with gemcitabine and
nab-paclitaxel, for front line treatment of locally-advanced pancreatic adenocarcinoma.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:
Secondary Outcome:
- Progression-free survival
- Local progression-free survival
- Objective response rate
- One-year survival rate
- Quality of life
- Pain-free survival
- Puncture-free survival
- Resectability rate
- Toxicity profile
PAST PRE-CLINICAL AND CLINICAL EXPERIENCE: The effect of the
electric fields (TTFields, TTF) has demonstrated significant activity in in
vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a
single modality treatment and in combination with chemotherapies. TTFields have
been demonstrated to act synergistically with taxanes and have been shown to be
additive when combined with other chemotherapies including gemcitabine. In
addition, TTFields have shown to inhibit metastatic spread of malignant
melanoma in in vivo experiment.
In a pilot study, 40 patients with locally advanced or metastatic pancreatic
adenocarcinoma received gemcitabine together with TTFields (150 kHz) or
gemcitabine and nab-paclitaxel together with TTFields (150 kHz) applied to the
abdomen until disease progression. The combination was well tolerated and the
only device-related adverse event was contact dermatitis.
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 2017).
DESCRIPTION OF THE TRIAL: All patients included in this trial are patients with
locally advanced pancreatic adenocarcinoma. In addition, all patients must meet
all eligibility criteria.
Eligible patients will be randomly assigned to one of two groups:
- Patients receive gemcitabine and nab-paclitaxel
in combination with TTFields using the NovoTTF-100L(P) System.
- Patients receive gemcitabine and nab-paclitaxel
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(P) group, the patients will be treated continuously with the
device until progression in the abdomen. On both arms, patients who have
progression outside the abdomen will switch to a second 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 pancreatic adenocarcinoma with very few side effects.
View this trial on ClinicalTrials.gov
