CLINICAL STUDY TO EVALUATE THE COLDPLAY CRYOBALLOON FULL AND SWIPE ABLATION SYSTEMS FOR THE ABLATION OF HUMAN ESOPHAGEAL EPITHELIUM IN PATIENTS UNDERGOING ESOPHAGECTOMY

Esophageal canceris the sixth leading cause of cancer death in the world .
Patients with Barrett*s esophagus have an increased risk for developing
esophageal adenocarcinoma. Malignant degeneration is believed to occur in a
stepwise fashion from nondysplastic intestinal metaplasia, to low-grade and
then high-grade dysplasia. Endoscopic surveillance to evaluate the progression
to dysplasia has become the standard of practice in the management of patients
with Barrett*s Esophagus.
The goal of therapy is the elimination of Barrett*s Esophagus (BE) and
restoration of squamous esophageal mucosal lining. Endoscopic treatments for
BE include Endoscopic Mucosal Resection (EMR) and/or endoscopic ablative
techniques based on cryogenic, thermal non-contact (such as argon plasma
coagulation - APC) or thermal contact (radiofrequency ablation - RFA)
technology. For visible lesions in BE, EMR is performed, while for high-grade
dysplasia in flat BE, ablative treatment is carried out. Moreover, a recent
study showed that ablation of low-grade dysplasia reduced the risk of
progression to high-grade or adenocarcinoma by 25%.
An important drawback of current available ablation techniques (RFA, APC) is
that they do not provide the necessary attributes for widespread adoption,
because of side effects, lack of predictability as to depth of ablation (as in
APC), length of procedure time, or cost (eg., inventory requirements, the need
for capital equipment).
C2 Therapeutics, Inc. (Redwood City, CA, USA) develops balloon-based
cryotherapy devices for the removal of unwanted tissue in endoscopic
procedures. The Coldplay CryoBalloonTM Ablation System provides controlled
cryotherapy ablation for the treatment of BE. Deployed through the working
channel of an endoscope, the Balloon is simultaneously inflated and cooled with
an inert cryogen (nitrous oxide) delivered from the Handle that ablates the BE
cells upon contact with the esophagus. After ablation, the Balloon is
repositioned for additional ablation or withdrawn. The System may allow for
potential benefits to the patient, the physician, and hospital, including a
shorter and safer procedure, an easier deployment reducing the need for
anaesthesiology, and smaller device inventory and no capital equipment
requirement
C2 Therapeutics has developed both a Swipe design (similar to the previous
Focal version) and Full design of the System. The Swipe design ablates an
area of approximately 90 degrees of the esophageal circumference (about the
size of a 20-cent Euro coin) and approximately 3cm in length. The Full System
is designed to apply refrigerant in a 360-degree pattern such that the entire
circumference of a specific length (approximately 3cm) of the esophagus is
treated with each application. The Swipe System and Full System are available
for investigational use only in the European Union (CE-mark is pending).
The Swipe System and Full System that are the focus of this study are the
second generation designs. The first generations of the systems were evaluated
in clinical studies:
1. The first generation Full System was evaluated in a prospective clinical
study that enrolled patients scheduled for esophagectomy for esophageal cancer
who agreed to have the cryoablation performed prior to their surgery. A total
of 21 ablations were performed in 13 patients. There were no adverse events.
Histological analysis confirmed that none of the ablation sites penetrated the
esophageal wall, and viable vasculature was present to the depth of the
submucosa in half of the specimens. Depth of injury (necrosis with or without
inflammation and edema) extended to the submucosa in ten of 21 of the ablation
sites; necrosis extended to the muscularis mucosa in one (1) patient.
2. The first generation Focal System was first evaluated in an extension to the
pre-esophagectomy study using the Full System. The Focal System was used to
treat four (4) patients. Subsequently, a prospective, multi-centre clinical
study enrolling 39 patients requiring treatment for Barrett*s Esophagus was
conducted. A total of 56 ablations were successfully performed. There were no
serious adverse events, and five (5) non-serious adverse events of mucosal
laceration that did not require treatment. Full squamous regeneration was seen
in 47 (85%) treated areas. These studies confirmed that ablation of unwanted
tissue in the esophagus using the CryoBalloonTM Focal Ablation System is
feasible and safe, and results in squamous regeneration in the majority of
patients.
While these studies confirmed the safety and performance of the CryoBalloonTM
Ablation Systems, the modified Full System and Swipe System have been developed
to improve the uniformity of refrigerant delivery and to increase the length of
esophageal tissue that can be treated in one application.

The primary objective of this study is to evaluate the safety and performance
of the CryoBalloon Ablation Systems (Full and Swipe) for the ablation of human
esophageal epithelium.

Prospective, non-randomised, single-centre single-arm study

Treatment with the Coldplay CryoBalloon Ablation Systems (Full and/or Swipe)

Complications specific to the CryoBalloon Full System include perforation or
laceration to the esophageal wall.

There is no direct benefit of study participation. However, other patients may
benefit in the future from what is learned as a result of this study.