ANET Electrosurgery Applicator Pilot Evaluation Study
Phase: NA
Conditions: Lung Cancer, Lung Cancer Metastatic
Sponsor: Olympus Corporation of the Americas

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CPR-05184AB 
Gyrus ACMI 
CPR-05184, Revision AB,  
ANET Electrosurgery Applicator 
Pilot Evaluation Study 
Health Canada Application #268397 
Gyrus ACMI, Inc., d/b/a Olympus Surgical Technologies America (OSTA) 
(formerly Spiration, Inc.) 
6675 185th Avenue NE 
Redmond, WA 98052 USA 
CERTIFICATION AND CONFIDENTIALITY AGREEMENT: 
I have read and agree to conduct this study in compliance with the approved 
investigational plan, Good Clinical Practices, and applicable regulatory requirements, as 
indicated by the investigator and the ethics committee. This investigational plan 
contains confidential proprietary information with respect to Spiration, Inc. products and 
this clinical study. 
______________________________________________ 
Print Name  
______________________________________________ 
________________ 
Signature of Investigator 
 
 
 
 
 
Date 
______________________________________________ 
Institution Name 
NCT03400748
01-Jun-2020

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ANET ELECTROSURGERY APPLICATOR PILOT 
EVALUATION STUDY 
STUDY OBJECTIVES 
Evaluate the preliminary safety and performance of the ANET 
Electrosurgery Applicator (ANET) during and after 
bronchoscopic ablation of a target pulmonary nodule/tumor. 
PRIMARY 
ENDPOINT 
Safety provided by the evaluation of peri-procedural, device-
related adverse events produced by the ANET device used to 
ablate a target pulmonary nodule/tumor. 
SECONDARY 
ENDPOINTS 
1. Pathological and histological evaluation of the acute 
thermal effect, produced by the ANET device, on targeted 
pulmonary nodule/tumor and surrounding tissue to 
determine if the observed zone of ablation is localized and 
consistent with the predicted zone of ablation. 
2. Characterize any effects on surrounding tissue outside the 
zone of predicted ablation. 
OBSERVATIONAL 
ENDPOINT 
Characterization of possible immune response changes. 
STUDY POPULATION 
Adult subjects with confirmed Stage I or Stage II primary lung 
cancer or metastatic lung tumor with a pulmonary 
nodule/tumor suitable for ablation by the ANET device via 
EBUS bronchoscopy, prior to planned surgical resection  
STUDY SIZE 
Up to 10 subjects will be treated, with interim evaluation after 
5 subjects have been treated.  
STUDY DESIGN 
This is a first in human use pilot study. Study subjects who 
are already scheduled for a surgical resection of their target 
nodule/tumor will be treated with the ANET RF Applicator. 
Blood will be drawn pre and post ablation, and at 2-4 weeks 
post-surgery. Following ANET ablation, the subject will 
undergo lung resection as scheduled. The ablated target 
nodule/tumor will undergo gross histopathologic assessment 
and may undergo immunohistochemical and 
microenvironment assessment for immune response.  
INCLUSION 
CRITERIA  
1. Subject with Stage I or Stage II primary lung cancer or 
metastatic lung tumor 
2. Pathological proof of target nodule/tumor type and 
malignancy 
3. Target nodule/tumor which can be accessed via EBUS 
bronchoscopy 
4. Resection/surgical candidate 
5. Participants must be at least 18 years old and able to 
provide consent 

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EXCLUSION 
CRITERIA 
1. Subjects in whom flexible bronchoscopy is contraindicated 
2. Target nodule < 1.0 cm  
3. Prior radiation or neo adjuvant chemotherapy of the target 
nodule/tumor 
4. Any comorbidity that the investigator feels would interfere 
with the safety of the subject or the evaluation of study 
objectives 
5. Pacemaker, implantable cardioverter, or other electronic 
implantable device 
6. Known or suspected sensitivity or allergy to nickel 
TREATMENT 
ALGORITHM 
The target nodule/tumor depth will be measured under EBUS 
visualization. The applied energy will be determined based on 
the nodule/tumor size using a pre-defined treatment algorithm 
to create a measurable and predictable ablation zones. A 
single ablation zone will be created in the first 3 subjects. The 
applied energy and number of ablation zones for the 
remaining subjects will be determined based on the 
nodule/tumor size and physician defined target ablation 
zone(s). 
PATHOLOGY 
ASSESMENT 
The ablated target nodule/tumor and surrounding tissue will 
be resected. The specimens will be examined by gross, 
histopathologic, and immune-histochemical methods. Routine 
staining will be performed with hematoxylin and eosin (H&E). 
Analysis of cellular vitality may be performed 
withimmunostaining, including mouse antihuman 
mitochondria monoclonal antibody (MAB 1273), TUNEL, 
Ki167,PHH3, and Masson’s trichrome. 
The pathology assessment will be performed by an 
experienced pathologist. 
IMMUNE RESPONSE 
Blood will be drawn pre and post ablation to assess immune 
response indicators. The microenvironment of the resected 
lung tissue may have pathological assessment for immune 
cell population to explore a potential mechanistic effect of 
immune response. 
FOLLOW-UP  
Subjects will be followed peri-operatively for safety. There is 
no long-term follow-up since the ablated tissue will be 
resected during the scheduled post-ablation surgical 
procedure, however adverse events will be captured 30 days 
post-procedure. There will be a blood draw 2-4 weeks 
following surgery, during the standard post-surgical visit. 

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1 
INTRODUCTION ...................................................................................................... 6 
2 
DEVICE DESCRIPTION .......................................................................................... 8 
2.1 Device Overview ................................................................................................ 8 
2.2 Handle ............................................................................................................... 9 
2.3 Needle (Proximal Electrode) ............................................................................ 10 
2.4 Coil (Distal Electrode) ...................................................................................... 10 
2.5 Ancillary Supplies............................................................................................. 11 
2.6 Packaging and Sterilization .............................................................................. 11 
3 
PRIOR ANIMAL STUDIES ..................................................................................... 12 
3.1 Rabbit Cancer Study ........................................................................................ 12 
3.2 GLP Swine Study ............................................................................................. 13 
4 
STUDY OBJECTIVES ............................................................................................ 16 
4.1 Objectives ........................................................................................................ 16 
4.1.1 Primary Endpoints ....................................................................................... 16 
4.1.2 Secondary Endpoints ................................................................................... 16 
5 
STUDY PLAN......................................................................................................... 17 
5.1 Study Design ................................................................................................... 17 
5.2 General Description of Study ........................................................................... 17 
6 
SUBJECT POPULATION ....................................................................................... 19 
6.1 Eligibility Criteria .............................................................................................. 19 
6.1.1 Inclusion Criteria .......................................................................................... 19 
6.1.2 Exclusion Criteria ......................................................................................... 19 
6.2 Assignment of Subject Identification ................................................................ 19 
7 
STUDY PROCEDURES AND PATHOLOGY METHODS ...................................... 20 
7.1 Informed Consent ............................................................................................ 20 
7.2 Procedure ........................................................................................................ 20 
7.2.1 Pre-ablation CT and blood draw .................................................................. 20 
7.2.2 ANET Procedure .......................................................................................... 20 
7.2.3 Post-ablation Bronchoscopic evaluation and CT ......................................... 21 
7.2.4 Post-ablation blood draw ............................................................................. 21 
7.2.5 Surgical Resection ....................................................................................... 21 
7.2.6 Pathology ..................................................................................................... 21 
7.2.7 Post-surgical blood draw .............................................................................. 22 
8 
ADVERSE EVENTS ............................................................................................... 23 
8.1 DEFINITIONS .................................................................................................. 23 
8.1.1 Serious Adverse Event (SAE) ...................................................................... 23 
8.2 Protocol Defined Potential Adverse Events ..................................................... 24 
8.3 Adverse Event Reporting ................................................................................. 25 
9 
PROTOCOL DEVIATIONS AND VIOLATIONS ..................................................... 26 
10 STUDY MANAGEMENT ........................................................................................ 27 
10.1 
Investigator Reports ..................................................................................... 27 
10.2 
Sponsor Reports .......................................................................................... 27 
10.3 
Clinical Study Monitoring Plan ..................................................................... 28 
10.3.1 Study Initiation Visits .................................................................................... 29 
10.3.2 Study Interim Visits ...................................................................................... 29 

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10.3.3 Study Closeout Visits ................................................................................... 30 
10.4 
Data Management Plan ............................................................................... 31 
11 STATISTICAL METHODS AND ANALYSIS .......................................................... 32 
 

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1 
INTRODUCTION 
The American Cancer Society's estimates for lung cancer in the United States for 2013 
are:  
• About 228,190 new cases of lung cancer will be diagnosed (118,080 in men and 
110,110 in women).  
• There will be an estimated 159,480 deaths from lung cancer (87,260 in men and 
72,220 among women), accounting for about 27% of all cancer deaths.  
Lung cancer is by far the leading cause of cancer death among both men and women. 
Each year, more people die of lung cancer than of colon, breast, and prostate cancers 
combined. 
Early detection, diagnosis and treatment of lung cancer is the largest unmet need in 
pulmonary medicine. Surgical resection is the treatment of choice for patients with 
Stage I and Stage II lung cancer1. However, over 20%2 are not suitable for resection 
due to comorbidities3. 
Localized energy destruction of tumors (ablation or coagulation) in other organs is a 
well-established technique, and initial feasibility pre-clinical and clinical evaluations have 
been performed in lungs.4,5 Percutaneous RF ablation is currently a therapeutic option 
for patients not appropriate for surgery, particularly individuals with poor pulmonary 
reserve6, however, treating central and hilar nodules and tumors with percutaneous RF 
is a contraindication for this therapy. 
Bronchoscopic ablation of lung cancer may provide benefits for patients not appropriate 
for or who decline surgery with Stage I or Stage II hilar/central tumors and nodules. 
 
1 Dennis A. Casciato, ed., Manual of Clinical Oncology, Seventh edition (Philadelphia: LWW, 2012). 
2 Amgad El-Sherif et al., “Outcomes of Sublobar Resection versus Lobectomy for Stage I Non-Small Cell 
Lung Cancer: A 13-Year Analysis,” The Annals of Thoracic Surgery 82, no. 2 (August 2006): 408-
415; discussion 415-416, doi:10.1016/j.athoracsur.2006.02.029. 
3 Jean Deslauriers MD FRCPS, F. G. Pearson MD, and Farid M. Shamji MD, Lung Cancer, Part I: 
Screening, Diagnosis, and Staging, An Issue of Thoracic Surgery Clinics, 1e, 1 edition (London: 
Elsevier, 2013). 
4 Hidemi Suzuki et al., “Innovative Technique of Transbronchial Radiofrequency Ablation for 
Intrapulmonary Tumors: A Preliminary Study in a Rabbit Model,” Journal of Bronchology & 
Interventional Pulmonology 18, no. 3 (July 2011): 211–17, doi:10.1097/LBR.0b013e318229671b. 
5 Ralf Eberhardt, Nicolas Kahn, and Felix J. F. Herth, “‘Heat and Destroy’: Bronchoscopic-Guided 
Therapy of Peripheral Lung Lesions,” Respiration 79, no. 4 (2010): 265–73, doi:10.1159/000284015. 
6 Thierry de Baere, Geoffroy Farouil, and Frederic Deschamps, “Lung Cancer Ablation: What Is the 
Evidence?,” Seminars in Interventional Radiology 30, no. 2 (June 2013): 151–56, doi:10.1055/s-
0033-1342956. 

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Lethal RF ablation zones extending beyond a tumor cannot adequately be 
characterized by imaging7. Therefore, “Treat and Resect” studies have been used to 
characterize tissue response to RF ablation of lung tissue. Jaskolka, et al8 studied 
patients in which metastases were resected 2-4 weeks after percutaneous RF treatment 
and demonstrated support for RF ablation as an effective treatment for select 
pulmonary metastases. Clasen, et al9 characterized the pathomorphology of tissue 
response for pulmonary malignancies treated with RFA, followed by resection 3 days 
later confirmed in their study that 10 (90.9%) cases of the tumor tissue was completely 
ablated, however in 2 cases a safety margin was absent. Schneider, et al10,11 
completed studies in which RF neoplasms were treated with RF intraoperatively, then 
immediately resected. In both studies they were able to histopathically characterize the 
ablation zone. Local control of the neoplasms was determined effective in 38% and 89% 
of the tumors treated, demonstrating that it should not replace surgery, but RFA was 
safe and may be an option for patients who are not candidates for surgery.  
 
7 Sophie Chheang et al., “Imaging Features Following Thermal Ablation of Lung Malignancies,” 
Seminars in Interventional Radiology 30, no. 2 (June 2013): 157–68, doi:10.1055/s-0033-1342957. 
8 Jeffrey D. Jaskolka et al., “Pathologic Assessment of Radiofrequency Ablation of Pulmonary 
Metastases,” Journal of Vascular and Interventional Radiology: JVIR 21, no. 11 (November 2010): 
1689–96, doi:10.1016/j.jvir.2010.06.023. 
9 Stephan Clasen et al., “Pathomorphologic Evaluation of Pulmonary Radiofrequency Ablation,” Cancer 
113, no. 11 (December 1, 2008): 3121–29, doi:10.1002/cncr.23882. 
10 Thomas Schneider et al., “Intraoperative Radiofrequency Ablation of Lung Metastases and Histologic 
Evaluation,” The Annals of Thoracic Surgery 87, no. 2 (February 2009): 379–84, 
doi:10.1016/j.athoracsur.2008.10.088. 
11 Jaskolka et al., “Pathologic Assessment of Radiofrequency Ablation of Pulmonary Metastases.” 

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2 
DEVICE DESCRIPTION 
2.1 Device Overview 
The Active Needle Endoscopic Treatment (ANET) Applicator is a disposable 
bipolar electrosurgical applicator used for the coagulation and necrosis of soft 
tissue. Each Applicator consists of a 19 gauge needle (proximal electrode) with a 
coil (distal electrode). The needle and coil serve as the bipolar electrodes, so there 
is no need for an external ground pad.  
The ANET Applicator works with ancillary equipment which include an ultrasound 
endoscope and a compatible electrosurgical generator. The ANET Applicator has 
been shown to be compatible with the previously cleared/approved Olympus ESG-
100 Electrosurgical Generator. Other radiofrequency generators will be added as 
compatibility is established. 
A standard infusion pump can be used to infuse small quantities of saline during 
active ablation. Saline is administered to cool the electrodes during ablation, and to 
prevent the tissue surrounding the target tissue from dehydration.  
To perform ablation, the flexible portion of ANET device is first inserted into an 
ultrasound endoscope with a working channel of 2.2mm, then locked onto the 
adapter biopsy valve on the endoscope using the endoscope adapter on the 
handle. The handle facilitates advancement of the sheath and needle (proximal 
electrode) during puncture of the target tissue. Once the needle is positioned in 
place, the handle is used to facilitate advancement and of the coil (distal 
electrode.) The distal electrode coils into the target tissue and helps to hold the 
device in place during treatment.  
To perform ablation, the bipolar plug on the ANET Applicator is connected to the 
compatible electrosurgical generator. The generator is set to the appropriate power 
level included in the Instructions for Use (IFU). During ablation, radiofrequency 
(RF) current is passed between the coil and the needle to thermally coagulate the 
tissue. Once the target energy has been reached, ablation is stopped and the coil 
and needle are retracted from the target. Additional ablations can be performed to 
achieve a larger coagulation zone. 

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Figure 1: ANET Applicator with Identification of All Components 
 
2.2 Handle 
The handle consists of the electrical and fluid connectors, the coil control, the 
proximal electrode control, the sheath control, and the endoscope connector 
(Figure 1). The handle includes error-proofing features assist the user in 
performing the advancement and retraction steps in sequence. 
An insulated bipolar plug connects the ANET to a compatible electrosurgical 
generator which delivers RF energy to the applicator. The saline line consists of a 
flexible silicon tube with standard luer fitting which delivers small quantities of 
saline through the needle tip during active ablation to cool the electrodes and to 
prevent tissue dehydration adjacent to the electrodes. The handle contains a 
saline manifold which routes saline from the saline line to the inside of the needle 
for delivery. 
The handle affixes to the endoscope via the connecting-slider, which locks the 
device onto the biopsy valve adapter. The needle control controls the needle’s 
extension out from the sheath. The proximal electrode can be advanced up to 
35mm from the sheath. The position of the needle relative to the sheath is 
indicated by the depth setter scale on the handle.  
The coil control advances and retracts the coil relative to the needle. Sheath  
The sheath, which houses the needle, consists of a single lumen, extruded PTFE 
tube. The sheath protects both the needle tip and endoscope during device 

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insertion into and retraction from the endoscope. The sheath also electrically 
insulates the electrodes from the endoscope (Figure 2). 
 
Figure 2: Sheath/Needle Tip 
2.3 Needle (Proximal Electrode) 
The needle is the proximal electrode. It is a19 gauge hypotube needle assembly 
located within the sheath. To penetrate the target tissue, the hypotube assembly is 
advanced beyond the sheath. The needle’s distal end is machined to a Huber point 
bevel form to easily penetrate through the tissue with minimal coring.  
The Huber tip is bent on the distal end to create a curved path. The curve is 
designed to orient the coil as it is advanced into the tissue. The 19G hypotube has 
several different laser cut patterns for added flexibility. A spiral cut on the distal 
portion of the 19G hypotube provides strength and flexibility during penetration into 
the target tissue. A laser cut “dog bone” pattern provides single plane bending and 
aligns the needlerelative to the endoscope during penetration. The laser cut region 
is fully covered by a layer of heat-shrink tubing to prevent saline leakage through 
the laser cuts and ensure that saline is delivered to the very distal end of the 
needle/electrode, where ablation is occurring. The most distal 9mm of the 19G 
hypotube has a shallow spiral groove on the outer surface, which reflects the 
endoscope’s ultrasound waves. The echo-enhanced region is intended to increase 
visualization at the tip, e.g., where the needle is located within the target tissue, 
and thereby help prevent penetration beyond the targeted tissue. 
After the needle tip has been inserted into the target tissue, the coil is advanced. 
The position of the needle tip determines where the coil will penetrate tissue.  
2.4 Coil (Distal Electrode) 
The coil is composed of an insulated Nitinol flat wire and extends the entire length 
of the device, through the inner lumen of the handle and needle.   
The distal end is formed into a coil shape to anchor the electrodes into the target 
tissue during coagulation. The tip of the coil is cut at a 45 degree angle to aid in 
tissue penetration. The coil portion has many shallow divot features, which reflects 
the endoscope’s ultrasound waves. The echo-enhanced region is intended to 

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increase the visualization of the coils, e.g., where the coil is located within the 
target tissue, and thereby help prevent penetration beyond the targeted tissue 
structure.  
The coil is gold plated from the proximal end point of the divots to the proximal end 
of the device; the purpose of the gold plating is to improve the conductivity of the 
coil. Due to the bipolar nature of the ANET device and the co-axial construction of 
the electrodes, the coil is electrically insulated from the needle with a polyethylene 
terephthalate (PET) heat shrink tubing.  
2.5 Ancillary Supplies 
• 
Electrosurgical generator - The ANET Applicator is compatible with the 
Olympus ESG-100 Electrosurgical Generator. Additional Olympus generators 
will be added via the 510(k) process as compatibility is established. 
• 
Ultrasound endoscope – The ANET Applicator is compatible with an ultrasound 
endoscope with an inner working channel of 2.2mm.  
• 
Olympus biopsy valve – Model # MAJ-1414  
2.6 Packaging and Sterilization 
In its packaged configuration, the device is held down to a card-stock backer card 
with ties and tabs. The device and backer-card is captured within a sealed pouch 
(made of LDPE and HDPE [Tyvek]), which is packaged inside a dust cover box. 
Each dust cover box contains one device inside a sealed pouch and an Instruction 
for Use (IFU).  
The device is sterilized by ethylene oxide (EO) sterilization.  

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3 
PRIOR ANIMAL STUDIES  
3.1 Rabbit Cancer Study 
Six rabbits (Oryctolagus cuniculus or similar) were inoculated with a VX2 cancer 
cells in the lower right lung approximately 10 days before the study. The 
inoculation was performed according to previously validated methods1. The test of 
ANET was performed under the TGH Preclinical Animal Study Protocol 
AUP4152.2. 
The power level for the ANET ablation was 10W and the saline flow rate was 30 or 
60 ml/hr. The target was evaluated using the EBUS bronchoscope (e.g. by 
ultrasound) to ensure visibility and accessibility for needle penetration and coil 
deployment. The number of pathlines was determined as shown in Figure 1. Once 
the ANET-EBUS needle was in the desired location, the electrode coil was 
advanced out of the needle into the target. Energy was continuously applied until 1 
kJ or the ESG stopped. After the desired energy was applied, the coil electrode 
was retracted into the needle. The needle was repositioned within the target to 
deliver additional energy applications as planned. After testing with the ANET 
device, the lungs were sectioned, fixed and stained at TGH. The sections were 
cryogenically fixed and stained using standard methods at TGH to evaluate the 
extent of coagulation necrosis12,13. 
  
 
12Neumann, R. A., Knobler, R. M., Pieczkowski, F. & Gebhart, W. Enzyme histochemical analysis of cell 
viability after argon laser-induced coagulation necrosis of the skin. Journal of the American 
Academy of Dermatology 25, 991–8 (1991). 
13Marcovich, R. et al. Optimal lesion assessment following acute radio frequency ablation of porcine 
kidney: cellular viability or histopathology? The Journal of urology 170, 1370–4 (2003). 

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Figure 3: Description of the Pathline technique used in this test 
 
Five of the rabbits had tumors that were cohesive and clearly visible under CT, and 
one animal had a very diffuse tumor (#214). Four of the 5 non-diffuse tumors were 
completely coagulated according to the histopathology data. In one animal, the 
target was well centered but did not coagulate enough tissue (#218).  
Target 
No 
Energy 
/Number of 
Activations 
Ablation 
time 
(minutes) 
Saline 
volume (ml) 
Ablated area 
measurement 
(long axis x 
short axis) 
Ablated 
Area* 
(cm2) 
Ablated area 
of tumor 
#212 
3.3kJ / 4 
activations 
13.6 
7.8 
1.8x0.8 
2.26 
100% 
#216 
4.3kJ /6 
activations 
14.8 
9.7 
2.0x1.4 
2.20 
100% 
#217 
4.6kJ / 6 
activations 
18.3 
13.6 
2.1x1.4 
2.30 
100% 
#218 
5.9kJ / 8 
activations 
15.3 
15 
2.6x0.8 
1.63 
45% 
#219 
2.2kJ / 4 
activations 
6.6 
7.2 
1.8x0.8 
1.13 
100% 
#214 
2.0 kJ / 2 
activations 
8.0 
4.1 
1.3x0.7 
0.741 
92% 
 
Table 1: Rabbit model ablation data 
The rabbit model data also showed that the saline flow did not result in any 
undesirable in or off-target effects and that the coagulation effect was confined as 
predicted. The rabbit data showed that the ANET device design and methods are 
capable of a significant and predictable thermal effect that inactivates tumor tissue. 
3.2 GLP Swine Study 
The primary goal of this GLP study was to evaluate the safety and efficacy of the 
test device (ANET RF applicator) to deliver energy into pseudo-tumors in swine 
lungs and produce a thermal effect without substantial concurrent damage to the 
surrounding healthy tissue.  
This GLP study was conducted under an IACUC approved protocol, SP-1602 GLP: 
RF Energy Ablation of Lung Pseudotumors Study in Yorkshire-Cross Farm Swine 
via Bronchoscopy (One Week Evaluation) and in accordance with Spiration’s 
protocol NCS-05097.AA. The study was conducted at the Care Research and 
Colorado Histo-Prep facilities in Fort Collins, CO. The protocol was executed 
without deviations and all amendments to the protocol after the release date were 
approved in advance by the study director and the sponsor’s representative and 
handled according to the released SOPs of CARE Research.  

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The test articles were ANET RF Applicator’s produced by Spiration Inc. The test 
subjects were 6 domestic swine with induced pseudo-tumors in the lungs. A total 
of 6 pseudo-tumors were ablated, 1 in each swine with 1 pseudo-tumor left un-
ablated in the opposite lung as a control. One extra animal was kept in reserve for 
the duration of the study as a backup. The pseudo-tumors were located and 
measured by EBUS bronchoscope and one per animal selected for RF ablation 
using the ANET RF applicator. The amount of energy delivered was based on the 
depth of the lesion as measured by EBUS, and determined by a predefined 
algorithm. During the thermal ablation the applicator electrodes are cooled with a 
flow of sterile physiological saline solution which conducts some of the heat away 
from the center of the bipolar ablation zone while also helping to maintain 
conductivity of the ablated tissue. With the rapid cooling of the saline as it expands 
away from the electrodes, no addition thermal tissue damage can be detected and 
the saline is absorbed by the tissue vasculature. The ANET applicators all 
functioned properly, and delivered the pre-determined amount of energy to the 
target location. Placement, visualization and subsequent removal of the electrodes 
in the pseudotumor targets was accomplished without complication. 
After ablations, the swine were recovered and monitored for peri- or post-
procedural complications and general health for 7 days, which according to the 
study pathologist was the optimal time to observe any cytocidal effects in the 
tissue. Each animal was then euthanized and a gross necropsy performed by the 
Study Board Certified Veterinary Pathologist. Lung tissue was removed, fixed, 
trimmed and processed into stained slides. The Study Pathologist then performed 
histopathological and histomorphometric evaluations of the H&E and trichrome 
stained slides and evaluated a panel of health screen organs for any findings.  
The animals were healthy for the duration of the study; all gained weight, and had 
hematology and clinical chemistry values which were consistent with animals in 
good health. 
The bronchoscopic follow up at 7 days revealed normal airways with only minimal 
hyperemia noted at the ablation penetration sites. At necropsy, direct observation 
of the thoracic cavity revealed no significant findings in 5 of the 6 swine, with only 
mild irregular consolidations in the lungs which were determined by the pathologist 
to be related to anesthesia and not the ablation procedure. One swine (1506) had 
chronic resolved pleuritis with adhesions and chronic resolved pericarditis with 
adhesions, both of which resulted from a prior infection that had resolved with no 
adverse effect on this study. This animal also had marked bilateral peri-acute 
alveolar hemorrhage with dorsal gravitational congestion due to the animal being 
on its back terminally. These findings were compatible with a terminal overdose of 
IV heparin with an extended period between the injection and euthanasia. No other 
gross findings were detected in either the thorax or the abdomen of the animals.  
Histopathology of the ablated pseudotumors and surrounding tissues revealed a 
localized thermal ablation effect with no evidence of adverse effects. There was 
some variation in the pattern of the thermal effect between different swine, 
however the surrounding vascularized pulmonary tissue rapidly cools the infused 
saline so that the ablation effects are limited to the target area and immediate 

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vicinity. There was no evidence of secondary bacterial infection in any of the 
bronchus penetration sites or in the ablated areas of the induced pulmonary 
pseudotumor. Where bronchoscopic observations implied thermal damage to the 
mucosa at the ANET penetration site, there was healing of the bronchus wall with 
active mucosal re-epithelization. This study demonstrates that even with site to site 
variation there is overall consistency in the ablation effects. These changes were 
focal and limited to the pseudotumor itself and the immediately surrounding 
tissues.  
In conclusion, peri and post procedural clinical observations, gross pathology and 
histopathological analysis indicate that the RF ablation provided by the ANET 
applicator is safe and effective in this model of pseudotumors, 7 days after its use. 

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4 
STUDY OBJECTIVES 
4.1 Objectives 
Evaluate the preliminary safety and performance of the ANET Electrosurgery 
Applicator (ANET) during and after bronchoscopic ablation of a target pulmonary 
nodule/tumor. 
4.1.1 Primary Endpoints 
Safety provided by the evaluation of peri-procedural device related adverse 
events produced by the ANET device used to ablate a target pulmonary 
nodule/tumor. 
4.1.2 Secondary Endpoints 
1) Pathological  and histologicalevaluation of the acute thermal 
effect, produced by the ANET device, on targeted pulmonary 
nodule/tumor and surrounding tissue to determine if the observed 
zone of ablation is localized and consistent with the predicted 
zone of ablation. 
2) Characterize any effects on surrounding tissue outside the zone 
of predicted ablation. 
4.1.3 Observational Endpoint 
1) Characterization of possible immune response changes. 

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5 
STUDY PLAN 
5.1 Study Design 
This is a first in human use pilot study. Study subjects who are already scheduled 
for a surgical resection of their target nodule/tumor will be treated with the ANET 
device. Following ANET ablation, the subject will undergo their scheduled lung 
resection. The ablated target nodule/tumor will undergo gross histopathologic 
assessment and may undergo immunohistochemical and microenvironment 
assessment for immune response. 
5.2 General Description of Study 
After consent and evaluation of all inclusion and exclusion criteria, subjects will be 
enrolled in the study. The subject will undergo standard pre-operative testing, per 
the study institutional requirements. At that time, subject vital signs will be 
recorded. The subject will be prepped for bronchoscopy.  
A pre-ablation chest CT will be taken. The target nodule/tumor will be accessed via 
EBUS bronchoscopy and ablated using the ANET Electrosurgical Applicator. 
Following ablation, there will be a bronchoscopic exam of the treated region and a 
repeat chest CT will be taken.  
Immediately following bronchoscopy and ablation of the target tissue, the subject 
will undergo the planned surgical resection. The ablated tumor will be prepared for 
histopathological and may be prepared for immunohistochemistry evaluation to 
assess the area of ablated tissue. Subjects will be followed peri-operatively. There 
is no long-term follow-up since the ablated tissue will be resected during the 
surgical procedure, however adverse events will be captured through 30 days post 
procedure. 
Blood will be drawn pre and post-ablation and 2-4 weeks post-surgery to evaluate 
for potential immune response indicators.  
 
 
 

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A study diagram is shown in Figure 4 below. 
 
 

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6 
SUBJECT POPULATION 
Adult subjects with confirmed Stage I or Stage II primary lung cancer or metastatic lung 
tumor with a pulmonary nodule/tumor suitable for ablation, by the ANET device via 
EBUS bronchoscopy, prior to planned surgical resection. 
6.1 Eligibility Criteria 
The criteria listed below shall be used to determine if an individual is eligible for 
enrollment in this clinical study. 
6.1.1 Inclusion Criteria 
1. Subject with Stage I or Stage II primary lung cancer or metastatic 
lung tumor 
2. Pathological proof of target nodule/tumor type and malignancy 
3. Target nodule/tumor which can be accessed via EBUS 
bronchoscopy 
4. Resection/surgical candidate  
5. Participants must be at least 18 years old and able to provide 
consent 
6.1.2 Exclusion Criteria 
1. Subjects in whom flexible bronchoscopy is contraindicated 
2. Target nodule < 1.0 cm  
3. Prior radiation or neo adjunctive chemotherapy of the target 
nodule/tumor 
4. Any comorbidity that the investigator feels would interfere with 
the safety of the subject or the evaluation of study objectives 
5. Pacemaker, implantable cardioverter, or other electronic 
implantable device 
6. Known or suspected sensitivity or allergy to nickel 
6.2 Assignment of Subject Identification 
Each subject who has signed an informed consent will be assigned a subject ID 
number unique to the subject and study site.  

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7 
STUDY PROCEDURES AND PATHOLOGY METHODS 
7.1 Informed Consent 
Subjects must sign the informed consent prior to enrollment. The original consent 
form will become an integral part of each case report form file. One copy will be 
retained with the subject’s medical records and one copy will be provided to the 
subject.  
7.2 Procedure 
All study eligible subjects will be prepared for the bronchoscopic/surgical 
procedure according to the policies and procedures established by the institution.  
Before starting the procedure a “time out” review will take place. During the “time 
out” session, the nodule/tumor to be treated will be noted by all in attendance.  
7.2.1 Pre-ablation CT and blood draw 
A pre-ablation chest CT will be taken prior to ANET ablation The CT may be 
taken while the subject is under general anesthesia. A pre-ablation blood 
draw will be also taken to assess for immune response indicators.  
7.2.2 ANET Procedure 
The ANET Applicator and RF generator will be prepared for use per the 
ANET Instructions for Use (IFU). The nodule/tumor will be accessed via 
EBUS bronchoscopy. If the nodule/tumor cannot be accessed via EBUS, or 
the nodule/tumor is considered inappropriate for ablation by the treating 
physician, the subject will proceed to surgery and will not count against 
enrollment. 
Under visualization with the EBUS bronchoscope, the needle path length of 
the nodule/tumor will be measured using the EBUS measurement tool. If the 
path length is less than 1 cm, then a new ablation zone in the target 
nodule/tumor will be identified. If an acceptable ablation zone cannot be 
determined, the subject will be considered a treatment failure and will not 
count against enrollment. Tissue ablation parameters will be determined by 
the IFU. 
The ANET applicator will be advanced to the target nodule/tumor under 
EBUS visualization. After the needle has been advanced into the target 
location, position may be confirmed using cone beam CT, intra-operative 
CT, or flouroscopy. The needle should be deep enough in the tissue and not 
extend past the distal margin of the target nodule/tumor. If it is not possible 
to place the needle appropriately, the subject will be considered a treatment 
failure. Once the needle is placed correctly, the target nodule/tumor will be 
ablated per the energy application guidelines in the IFU 
 
 

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7.2.3 Post-ablation Bronchoscopic evaluation and CT 
A post-ablation Bronchoscopic evaluation and chest CT will be taken 
following ANET ablation, while the subject is under general anesthesia. 
7.2.4 Post-ablation blood draw 
A post-ablation blood draw will be taken to assess for immune response 
indicators.   
7.2.5 Surgical Resection 
Surgical resection will be performed as scheduled, per institutional 
guidelines.  
Following resection, the ANET ablated tumor will be grossly evaluated and 
prepared for pathologic evaluation of the treated tumor. 
7.2.6 Pathology 
The tumors will be bisected through the largest diameter in a right angle 
referring to the RFA electrode direction and marked to determine orientation 
of coagulation electrode immediately after the resection procedure. The 
specimens will be fixed in 10% neutral buffered formalin-solution and 
prepared for routine diagnostics and immunohistochemistry. 
The specimens will be examined by gross pathology, histopathology, and 
may be examined by immunohistochemical methods. Routine staining will 
be performed with hematoxylin and eosin (H&E). Analysis of cellular vitality  
be performed of immunostaining, including mouse antihuman mitochondria 
monoclonal antibody (MAB 1273; Millipore UK, Hertfordshire, UK)14,15, 
Terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL; 
Boehringer Ingelheim, Germany),16 antibody MiB1(Ki67; Dianova, Hamburg 
Germany)17 ,18and PHH319, and Masson’s trichrome2021. The 
 
14 Schneider et al., “Intraoperative Radiofrequency Ablation of Lung Metastases and Histologic 
Evaluation.” 
15 Thomas Schneider et al., “The Efficacy of Bipolar and Multipolar Radiofrequency Ablation of Lung 
Neoplasms - Results of an Ablate and Resect Study,” European Journal of Cardio-Thoracic Surgery: 
Official Journal of the European Association for Cardio-Thoracic Surgery 39, no. 6 (June 2011): 
968–73, doi:10.1016/j.ejcts.2010.08.055. 
16 Clasen et al., “Pathomorphologic Evaluation of Pulmonary Radiofrequency Ablation.” 
17 Ibid. 
18Pelosi et al. J Thorac Oncol. 2014;9: 273–284 
19 Ozturk Sari et al. Endocr Pathol. 2016 Ju=n;27(2):162-70 
20 Jie Ouyang et al. Utility of desmin and a Masson’s trichrome method to detect early acute 
myocardial infarction in autopsy tissues, Int J Clin Exp Pathol 2010;3(1):98-105. 
21 T.D. Koreckij et al., Low Dose, Alternating Electric Current Inhibits Growth of Prostatic 
 

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immunohistochemical criterion for cell death in is the lack of expression or 
proliferation/mitotic index markers in the treated and surrounding tissue. The 
intent of the pathology assessments is to determine if the observed zone of 
ablation is consistent with the predicted zone of ablation and to characterize 
any effects on surrounding tissue outside the zone of predicted ablation. 
The micro environment of the resected tissue may have pathological 
assessment for immune cell population to explore a potential mechanistic 
effect of  immune response.22. 
The pathologic and immunohistochemical effect of RFA on nodules/tumors 
and surrounding tissue will be evaluated by an experienced pathologist.  
7.2.7 Post-surgical blood draw 
A post-surgical blood draw will be taken 2-4 weeks post-surgery to assess 
for immune response indicators. 
 
Cancer, The Prostate, Accepted 5 October 2009, Published online in Wiley InterScience 
(www.interscience.wiley.com). 
22 M.A.J. Gorris, et al. Eight-Color Multiplex Immunohistochemistry for Simultaneous Detection 
of Multiple Immune Checkpoint Molecules within the Tumor Microenvironment J Immunol 
January 1, 2018, 200 (1) 347-354 

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8 
ADVERSE EVENTS 
Peri- procedural adverse events, defined as from the start of the EBUS bronchoscopy 
through the planned surgical resection, up to 30 days post procedure will be collected,. 
Adverse events shall be reported in accordance with study institution requirements, 
local vigilance systems, sections 59 to 62 of the Canadian Medical Device Reporting 
Regulations, and ISO 14155:2011, sections 8.2.5 and 9.8.  
8.1 DEFINITIONS  
8.1.1 Adverse event: Any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the investigational 
medical device which includes:  
a. events related to the investigational medical device or the comparator; and 
b. events related to the procedures involved 
For users or other persons, this definition is restricted to events related to 
investigational medical devices.  
 
8.1.1 Serious Adverse Event (SAE)  
Adverse event that: 
a) led to a death, 
b) led to a serious deterioration in health that either: 
1) resulted in a life-threatening illness or injury, or 
2) resulted in a permanent impairment of a body structure or a body 
function, or 
3) required in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) resulted in medical or surgical intervention to prevent life 
threatening illness or injury or permanent impairment to a body 
structure or a body function. 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect. 
NOTE 1: This includes device deficiencies that might have led to a serious 
adverse event if a) suitable action had not been taken or b) intervention had 
not been made or c) if circumstances had been less fortunate. These are 
handled under the SAE reporting system. 
NOTE 2: A planned hospitalization for pre-existing condition, or a procedure 
required by the Clinical Investigation Plan, without a serious deterioration in 
health, is not considered to be a serious adverse event. 

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8.2 Protocol Defined Potential Adverse Events 
The following list of adverse events are anticipated given the nature of the EBUS 
procedure and the investigational device.  
Table 2: Potential Adverse Events 
MedDRA term 
 
Term type 
Term ID 
Ablation site reactions 
including… 
 
HLT 
10021544 
 
Ablation site reaction 
PT 
10021542 
Abscess formation 
 
LLT 
10058042 
Anesthetic complications 
 
HLT 
10002111 
Arrhythmia 
 
PT 
10003119 
Atelectasis 
 
PT 
10003598 
Bronchopulmonary hemorrhage 
PT 
10065746 
Bronchospasm 
 
HLT 
10006482 
Bronchial obstruction 
 
PT 
10006440 
Burn or charring outside of 
ablation zone 
 
PT 
10006706 
Cardiac arrest 
 
PT 
10007515 
Death 
 
PT 
10011906 
Device failure 
 
PT 
10018065 
Dyspnea 
 
PT 
10013968 
Electric shock 
 
LLT 
10014357 
Hematoma 
 
PT 
10055370 
Hemoptysis 
 
PT 
10018964 
Hemorrhage 
 
PT 
10019524 
Hemothorax 
 
PT 
10019614 
Hypoxemia 
 
LLT 
10021142 
Infection (acute) 
 
PT 
10076200 
Laryngeal spasm 
 
LLT 
10023854 
Pleural effusion 
 
PT 
10035598 
Pleural hemorrhage 
 
PT 
10055319 
Pleuritic pain 
 
PT 
10035623 
Post-procedural hemorrhage 
 
LLT 
10055322 
Post-procedural thoracic complication 
PT 
10056745 
Pneumonia 
 
PT 
10035664 
Pneumonitis 
 
PT 
10035742 
Pneumo-mediastinum 
 
LLT 
10050184 
Pneumothorax 
 
PT 
10035759 
Pulmonary edema 
 
PT 
10037375 
Pulmonary embolism 
 
PT 
10050071 
Pulmonary fistula 
 
PT 
10065873 
Respiratory failure 
 
HLT 
10038695 
Tissue necrosis 
 
PT 
10065769 
Traumatic lung injury 
 
PT 
10022117 
Tumor seeding 
 
LLT 
10049737 
Tumor recurrence 
 
LLT 
10029097 

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8.3 Adverse Event Reporting 
The investigator is required to report a serious adverse event, regardless of 
whether the event is considered anticipated or unanticipated based on the 
defined potential adverse event list in Table 2, to Health Canada and to the 
manufacturer and importer within 72 hours of discovery. This includes cases 
in which the incident:   
o is related to a failure of the device or a deterioration in its effectiveness, or 
any inadequacy in its labelling or in its directions for use, and   
o has led to the death or a serious deterioration in the state of health of a pa
tient, user or other person, or could do so were it to recur.  
 
For an incident that occurs in Canada, the manufacturers and importers are 
required to provide a preliminary and a final report in respect of the incident. 
The preliminary report shall be submitted: 
• Within 10 days after the manufacturer or importer of a medical device 
becomes aware of an incident, if the incident has led to the death or 
a serious deterioration in the state of health of a patient, user or other 
person, or  
• Within 30 days after the manufacturer or importer of a medical device 
becomes aware of an incident, if the incident has not led to the death 
or a serious deterioration in the state of health of a patient, user or 
other person, but could do so were it to recur.   
 
 

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9 
PROTOCOL DEVIATIONS AND VIOLATIONS 
During the course of the study, any deviations or violations from this protocol will be 
properly logged and documented by the site. 

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10 STUDY MANAGEMENT 
The clinical study will be conducted in accordance with the applicable Sponsor SOPs.  
The sponsor will establish a clinical study plan that is appropriate to this study and that 
ensures compliance with  Health Canada) regulations, Good Clinical Practice (GCP), 
and any other applicable regulations. 
 
The clinical study plan will establish and document practical working methods for the 
management and execution of the pivotal study.  The plan will address study-specific: 
definitions, roles, responsibilities, documents, clinical site and investigator selection, site 
qualification, training, inventory management, CRO management, data management, 
clinical data and CRFs, safety reporting/AEs/SAEs, monitoring, randomization, record 
retention, clinical complaints and product returns, and applicable sponsor SOPs and 
work instructions. 
10.1 
Investigator Reports 
All study investigators shall prepare and submit the following complete, accurate, and 
timely reports.  
1) Serious adverse events: An investigator shall submit to the sponsor, Health 
Canada and to the reviewing REB a report of any serious adverse event 
occurring during an investigation as soon as possible, but in no event later than 
72 hours after the investigator first learns of the effect. See section 8.3 for 
reporting parameters.  
2) Deviations from the investigational plan.  
10.2 
Sponsor Reports 
The study sponsor shall prepare and submit the following complete, accurate, and 
timely reports and revised authorizations:   
1) Adverse events:  Please see section 8.3 for reporting parameters.   
2. Manufacturers or importers may submit a request for a revised authorization to 
address changes made to the device, study investigation plan, or institutional 
information, such as those listed below: 
a. A change to the device  
o A change involving modifications to device design (where the device 
generally maintains its original functionality and intended use), 
sterilization, software, materials, and/or labelling 
o A change in device name or device identifier 
o A change to the number of devices requested 
o A change to the manufacturer name 
b. A change to the study documents (protocol and ICF)  
o A change to the study protocol that will not bias the data previously 
collected (see list of examples below) 
o ICF revisions (clarifications to language/wording) 

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o Additional study subjects 
o Change to duration of study 
c. A change to the institutional information  
o Addition or removal of institutions where the testing is being conducted 
o Change to the list of qualified investigator(s) 
o Updated REB approval information  
Examples of protocol changes that would require a revised authorization are listed 
below. When in doubt whether an application is required, sponsors should contact the 
Investigational Testing Division at: hc.it-ee.sc@canada.ca. 
1. Protocol revisions to permit the enrolment of additional study subjects and longer 
term patient follow-up. 
2. Any protocol amendment that requires REB approval will also require a Health 
Canada authorization. 
3. Inclusion and exclusion criteria modifications. These include changes to eligibility 
criteria, tests or procedures for selecting the study population, as well as tests, 
procedures, or criteria for dismissing clinical trial subjects prematurely or at the 
end of the trial. 
4. Changes to the patient selection criteria, tests or procedures required for the 
ongoing assessment of clinical trial subjects, including assessment of safety, or 
evaluation of safety and effectiveness. This includes protocol changes as a result 
of serious unexpected adverse reactions. 
5. Inclusion of sub-studies. 
6. Changes to sample size estimation or addition of interim analyses that will affect 
the analysis and interpretation of the study results. 
7. Changes to the post-treatment follow-up period that may affect the safety 
evaluation of the device. 
8. Use of ancillary medical devices for the treatment or monitoring of the study 
subjects that may have an impact on the analysis of effectiveness or increase the 
risk to clinical trial subjects. 
9. Changes to the requirements or procedure for reporting of serious, unexpected 
adverse reactions. 
10.3 
Clinical Study Monitoring Plan 
Regular monitoring of study data at each site will be performed as defined by the study 
specific clinical plan.  Individual sites will be monitored to verify that enrollment rate, 
data recording, and protocol adherence are satisfactory.  The frequency of monitoring 
individual sites will fluctuate depending on enrollment rate and site performance.  The 
details of frequency of visits, activities to be performed at each visit, etc., are part of the 
conduct of the study, and will be implemented on an ongoing basis during the course of 
the study, in accordance with the monitoring procedures and the study specific clinical 
plan. 
Monitoring visits will be performed for the purposes of verifying adherence to the 
protocol and the completeness and accuracy of data entered on the CRF.  The study 
monitor will verify CRF entries by comparing them with the primary source documents 

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(hospital/clinic/office records), which will be made available for this purpose.  The 
monitor will review the maintenance of regulatory documentation, device accountability, 
and any protocol deviations and/or violations.  The monitor will also review the progress 
of the study with the investigator and other site personnel on a regular basis.  At the end 
of the study, a close-out monitoring visit will be performed.  Monitoring visits will be 
arranged in advance with site personnel at a mutually acceptable time.  Sufficient time 
must be allowed by the site personnel for the monitor to review CRFs and relevant 
source documents.  The coordinator and/or investigator should be available to answer 
questions or resolve data clarifications. 
Monitoring visits will include study initiation visits, ongoing monitoring visits and study 
close-out visits, as described in the following sections. 
10.3.1 
Study Initiation Visits 
The study monitor or designee will communicate with study site and identify a date, time 
and location to meet with the clinical investigator(s), coordinator, and other key 
personnel involved in the study.  A memo will be distributed to all key personnel 
confirming the date, time, location and purpose of the visit along with a detailed agenda. 
Prior to the study initiation site visit, the clinical site should submit the following 
documents to the study monitor, or have them available for collection during the visit: 
• Signed Investigator Agreement, 
• Curriculum vitae of investigator, 
• Medical license of investigator, 
• Signed Financial Disclosure Form, and 
• REB/Ethics committee approval documentation of protocol and informed consent 
form. 
 
The study monitor will review the study protocol requirements with special emphasis on 
the inclusion and exclusion criteria, study objectives, safety and efficacy endpoints, AE 
reporting, participant withdrawal criteria, the visit schedule and required assessments, 
special clinical procedures, study stopping rules, and other key site requirements for 
study support. 
The study monitor will review the site’s procedures for obtaining and documenting the 
participant’s informed consent, including who is responsible for this process and the 
location of the completed forms.  A thorough review of the regulatory binder with site 
staff and investigator will be performed for completeness.  The study monitor will review 
the protocol case report forms and the site’s plans for maintaining adequate source 
documentation.   
10.3.2 
Study Interim Visits 
The first monitoring visit after site activation normally will be conducted when the first 
few participants have been enrolled at the site.  Since study monitoring is based on the 
rate of patient enrollment, the number of patients enrolled at each site, and a number of 

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other variables, monitoring will be adjusted to reflect the needs of the study and the 
participating sites.   
Prior to the site visit, the study monitor will review the protocol for critical aspects of the 
study for monitoring compliance.  The study monitor will also review outstanding queries 
and missing forms, unresolved issues from the previous site monitoring visit (if 
applicable), study signature log, regulatory checklist, and device accountability log, as 
well as any other project specific documents. 
The study monitor will review demographic and eligibility criteria source documentation 
to ensure that all participants who have been enrolled in the trial were eligible.  All data 
or events that: 1) are critical to the reliability of the study findings, specifically those data 
that support primary and secondary endpoints, 2) are critical to the safety and ethical 
treatment of study subjects, or 3) affect the integrity of critical data will be 100% source 
verified.  If possible, identified discrepancies will be corrected by the site staff during the 
visit, but may be corrected afterwards.  Documentation will also be reviewed for AEs.  
Any protocol deviations or unreported AEs will be brought to the attention of the 
coordinator and/or investigator for immediate action.  The study documentation to be 
kept in the study regulatory binder will also be reviewed routinely. 
Informed consent forms will be reviewed to verify that the appropriate REB/IEC 
approved consent has been signed by both patient and the person administering the 
consent, dated, and properly witnessed if this is required by the form used at the site.  
Test articles will be reviewed at each visit and compared to the test article accountability 
log.  The study monitor will be responsible to review the delivery and the inventory 
records to ensure that the quantity of the study product was shipped, received or 
returned as specified.  The test article records will be compared with the participant 
records to ensure that proper device was received.  The monitor will also verify that the 
test article is kept in a secure locked place.   
The study monitor will conduct a summary meeting with the study investigator and/or 
the study coordinator to discuss the findings of the monitoring team, discrepancies 
found, corrected, and remaining, and any recommendations to improve data quality for 
future site visits.  An attempt should be made to correct any discrepancies found on the 
case report forms or in the source documentation.  These discrepancies will still be 
included in the monitoring report, as well as whether resolved or in need of resolution 
after the monitoring visit.  In addition, the overall status of enrollment, amendments, and 
other protocol adherence issues are to be addressed. 
After the interim site monitoring visit, the site will receive a summary of any data 
discrepancies as well as any other issues encountered.  The summary will also describe 
any outstanding issues that will require the site’s attention. 
10.3.3 
Study Closeout Visits 
The study closeout visit will occur once all subjects have completed the study through 
the peri-procedure follow-up phase and all data is collected (i.e.; pathology).  A study 

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closeout visit will include all of the elements identified as part of the interim monitoring 
visit information.  It will also include a review of data not previously audited. 
The study monitor will conduct a summary meeting with the study coordinator and the 
study investigator to discuss any discrepancies or other findings by the monitoring team.  
At this meeting, an attempt should be made to resolve discrepancies in the source 
documentation requiring the investigator’s revision.  The study monitor will also review 
all regulatory requirements the site may have for closing this study with their REB and 
for the maintenance and retention period of study documentation. 
A closeout site visit report will be prepared, with all outstanding issues listed.  The site 
should resolve all issues within a reasonable time after the visit.  Once the study 
monitor verifies that all open issues are resolved, the site will be considered closed.   
10.4 
Data Management Plan 
The sponsor will establish a data management plan that is appropriate to this study and 
that ensures the protection of human subjects, protocol compliance, data accuracy, and 
data integrity. 
Study data will be collected in accordance with Good Clinical Practice. Written Case 
Report Forms (CRFs) will be used to collect subject data. The bronchoscopy procedure 
may be video recorded.  
A core pathology lab may be used for gross pathology, histopathology, immune-
histopathology, and micro CT analysis of the ablation zone.  A core lab will be used for 
analyzing blood for possible immune response.  The core labs will collect data in 
accordance with Good Clinical Practice. 
 

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11 STATISTICAL METHODS AND ANALYSIS 
This is a pilot study with primary outcomes aimed at collecting adverse event 
information. Summary results will be reported, as there is no proposed hypothesis. The 
sample size of 10 has been arbitrarily chosen to provide procedural and device related 
adverse event information. Subjects who are considered “Treatment Failures” will not be 
counted against the sample size of 10.