Clinical trial NCT01331863: Airway and/or Pulmonary Vessels Transplantation
Official title: Replacement of the Airways and/or the Pulmonary Vessels Using a Cryopreserved Arterial Allograft
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Tracheal Neoplasm
Tracheal Stenosis
Keywords: Bronchial disease
Lung cancer surgery
Aorta/aortic Allograft
homograft
Tracheal disease
Benign
Malignant
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2011-04-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: * First study (BRONC-ART) The purpose of this prospective study is to evaluate the 90-day morbidity and mortality rates of bronchial transplantation using cryopreserved aortic allograft in proximal lung cancer surgery. The investigators hypothesize that this stage 1-2 surgical innovation could be safe and effective in order to reduce the 90-day morbidity and mortality rates compared to those observed with pneumonectomy, especially when some factors are present: age \> 70 years, right side, neoadjuvant chemoradiotherapy.
* Current study (TRACHEO BRONC-ART) The BRONC-ART study was extended to major (malignant or benign) lesions of the trachea requiring airway transplantation.

For these patients, resection followed by direct end to end anastomosis is not possible or at high risk.

Detailed description: Surgery remains the best option for curative treatment of early stages Non-Small Cell Lung Cancer (NSCLC). Peripheral tumors are usually resected using lobectomy with a low 90-day morbidity and mortality rate (2%). Central NSCLC often require a pneumonectomy with a high 90-day morbidity and mortality rate (up to 24%), especially when some factors are present: age \> 70 years, right side, neoadjuvant chemoradiotherapy. On the other hand, bronchoplastic lobectomies have been proposed in order to avoid pneumonectomy. However, more than fifty years after their first description, bronchoplastic lobectomies remain uncommon (\<1% of all pulmonary resection). This could be explained by some technical difficulties showing the potential interest of a bronchial substitute. In a 10-year research phase on a sheep model (n=108), we demonstrated that aortic grafts could be valuable substitutes for tracheobronchial replacement. We observed a progressive transformation of the aortic tissue into airway tissue comprising epithelium and regenerated cartilage. The technique was extended to clinical tracheal replacement by us and others with encouraging results. We proposed to evaluate the feasibility of the use of a stent-supported cryopreserved aortic allograft as a bronchial substitute to prevent pneumonectomy and its associated high mortality rate in NSCLC surgery. Primary outcome will be the 90-day mortality. Secondary outcomes will be the postoperative complications, the 90-day morbidity. This prospective open study will include 20 to 30 patients according to eligibility criteria (see below). The operation will consist of the curative resection of the NSCLC followed by the replacement of a bronchial segment using a cryopreserved allograft in order to re-implant a functional pulmonary lobe. A stent will be placed in the graft to prevent airway collapse.

-Current study (TRACHEO BRONC-ART) The BRONC-ART study was extended to major (malignant or benign) lesions of the trachea requiring airway transplantation. For these patients, resection followed by direct end to end anastomosis is not possible or at high risk.

Eligibility criteria: Inclusion Criteria:

* patient age ≥18 years and patient capable of giving consent to the carrying out of a medical research procedure
* patient with proximal Lung Cancer (LC) requiring surgical resection (carinal resection, pneumonectomy, bronchoplastic lobectomy) after neoadjuvant chemotherapy or not and with adequate preoperative lung function tests
* or patient with proximal LC requiring a pneumonectomy without adequate preoperative lung function tests
* patients with extended lesions malignant or benign of the trachea without bronchitic lesion and who are in therapeutic impasse.
* or patient older than 70 years with proximal LC requiring a pneumonectomy
* decision made by a multidisciplinary team
* patient information and consent

Exclusion Criteria:

* patient age \< 18 years or patient not capable of giving consent to the carrying out of a medical research procedure
* patient with proximal or peripheral LC requiring a simple lobectomy
* patient with unresectable LC because of major local involvement, N3 and/or M1 status(with the exception of a unique resectable brain metastasis)
* patient with tracheal lesion that can be isolated from a simple resection anastomosis tracheal
* iodine allergy
* preoperative evaluation not allowing a simple lobectomy
* patient not affiliated to the French Social Security System

Primary outcomes:
measure: 90-day mortality
timeFrame: 3 months
Secondary outcomes:
measure: 90-day morbidity
timeFrame: 90 days
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, CHU Paris-Seine-Saint-Denis
state: Seine-Saint-Denis
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Emmanuel MARTINOD, Pr, PhD
role: STUDY_DIRECTOR
References:
citation: Martinod E, Chouahnia K, Radu DM, Joudiou P, Uzunhan Y, Bensidhoum M, Santos Portela AM, Guiraudet P, Peretti M, Destable MD, Solis A, Benachi S, Fialaire-Legendre A, Rouard H, Collon T, Piquet J, Leroy S, Venissac N, Santini J, Tresallet C, Dutau H, Sebbane G, Cohen Y, Beloucif S, d'Audiffret AC, Petite H, Valeyre D, Carpentier A, Vicaut E. Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices. JAMA. 2018 Jun 5;319(21):2212-2222. doi: 10.1001/jama.2018.4653.