TruFreeze™ Airway Obstruction: TAO STUDY

A PROSPECTIVE, MULTI-CENTER PILOT STUDY OF THE truFREEZE™ SYSTEM TO ASSESS THE EFFICACY AND SAFETY OF CRYO SPRAY ABLATION IN THE TREATMENT OF AIRWAY OBSTRUCTIONS (TruFreeze AIRWAY OBSTRUCTION - "TAO" STUDY)

The purpose of this study is to prospectively assess the efficacy and safety of spray cryotherapy ablation with the truFreeze System in conjunction with mechanical dilation or debridement for the treatment of clinically significant obstructions of the central airways. The primary effectiveness endpoint is the proportion of subjects with a minimum of 25% improvement in luminal patency following SCT treatment and mechanical intervention 30 days (+/- 5 days) following treatment. Additionally, a primary clinical safety endpoint is the reporting of all adverse events.

This multi-center prospective feasibility study will enroll at up to 6 clinical sites for a total of 30 subjects. Enrollment criteria includes subjects with clinically significant benign or malignant obstructions of the central airways, who require treatment intervention and are not candidates for surgical resection. The central airways are defined as including the trachea, left or right main bronchus, or the bronchus intermedius on the right. Spray cryotherapy (SCT) using the truFreeze system will be used in conjunction with mechanical interventions (balloon/rigid dilation or debridement of tumors) to improve airway patency. Subjects will receive up to 4, 5-second spray cycles prior to mechanical intervention (balloon/rigid dilation or debridement of tumors), followed by up to 4, 5-second additional spray cycles immediately following mechanical intervention.

The degree of airway narrowing will be estimated by the treating physicians before and after each treatment using a graded scale. Digital endoscopic images of each obstruction taken before and after each treatment, will also be assessed by a neutral assessor blinded to treatment. Subjects will be contacted on Day 1 following treatment to assess for any treatment related adverse events. Subjects may undergo a repeat bronchoscopy two weeks (14 days +/- 2 days) following the initial SCT treatment if clinically indicated or routine practice of the treating physician. A SCT treatment at a NORMAL flow setting may be performed at the 14 day bronchoscopy if deemed clinically indicated. If subjects are treated with SCT at the 14-day treatment, they will again be contacted on Day 1 following treatment to assess for any treatment related adverse events.

A follow-up bronchoscopy to reassess luminal patency and treatment site healing response will be performed at 30 days (+/- 5 days) following the last SCT treatment. The last SCT treatment may be the initial treatment day or 14-day treatment if performed. again, the degree of airway narrowing will be estimated by the treating physicians using a graded scale and digital endoscopic images of each obstruction will be taken to be assessed by a neutral assessor blinded to treatment.

The primary efficacy endpoint for statistical analysis and study powering will be the proportion of subjects exhibiting an adequate (minimum of 25%) improvement in airway patency. Based on prior clinical experience with liquid nitrogen spray cryotherapy and other ablation techniques, a response rate of approximately 80% is anticipated. This study is powered to detect a 20% lower response rate (i.e. 60% or lower) compared to the expected rate.

Inclusion Criteria:

1. Subjects with symptomatic, clinically significant central airway obstruction requiring treatment intervention and who are not candidates for surgical resection. The central airway obstruction must be a consequence of any of the following:

   1. Benign airway strictures
   2. Primary or secondary endobronchial tumors located in the central airways
   3. Airway stents complicated by significant granulation tissue

2. Subjects (or designated proxies) who are able to provide written informed consent

3. Subjects aged 18 years or greater

4. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less

5. Subjects deemed eligible candidates for spray cryotherapy based on medical history and physical exam

Exclusion Criteria:

1. Subjects undergoing treatment with any other investigational therapy within the month preceding cryotherapy or planned within 1 month following treatment

   a. Subjects with malignant strictures who require chemotherapy/radiation therapy (including investigational therapies) within 30 days will be allowed participation in the study.

2. Subjects with extraluminal causes of airway obstruction such as bulky mediastinal adenopathy, or a central mediastinal tumor causing compression of the airway

3. Subjects with less than 3 month expected survival

4. Subjects who it is anticipated will require stent placement during their initial treatment

5. Subjects who are pregnant or nursing, per device instructions for use

6. Subjects (or a designated proxy) who are unwilling to provide written informed consent

7. Subjects with ECOG performance status greater than 3

8. Subjects likely to have difficulty complying with study visit follow-up scheduling

9. Known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions related to informed consent, post-treatment instructions, or follow-up

10. Subjects with uncontrolled coagulopathy or other bleeding disorders