Tracheal Replacement Using A Cryopreserved Aortic Allograft For R0 Resection In Locally Advanced Thyroid Cancer (TRITON 02 Tracheal Replacement In ThyrOid caNcer)

NCT07823686 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP200131
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Airway transplantation remains a great surgical and biological challenge. This is still an unsolved problem for patients in therapeutic impasse because of major tracheobronchial lesions requiring surgical resection and airway reconstruction. Schematically, 5 principal ways of research have been explored with the use of synthetic prostheses, airway bio-prostheses, tracheal allografts, various autologous substitutes and more recently bio-engineered conduits. The lack of prospective human studies did not allow standardizing surgical approaches. Since 1997, airway bioengineering using aortic grafts as biological matrices, has been tested in our laboratory (Alain Carpentier Foundation) as a potential solution to the unsolved problem of tracheobronchial replacement. Preclinical studies showed that autologous aortic grafts, fresh and cryopreserved aortic allografts could be valuable tracheobronchial substitutes. The progressive regeneration of both epithelium and cartilage within the aortic matrices from recipient progenitor/stem cell homing permitted the restoration of new functional airways. These results allowed clinical applications in patients with extensive tracheal diseases or lung neoplasms. Recently the feasibility of this innovative approach using stented -80°C CAA was demonstrated in a prospective study including 20 patients (NCT01331863; Martinod E et al. Feasibility of bioengineered tracheal and bronchial reconstruction using stented aortic matrices. JAMA 2018;319:2212-22). Two patients included in the series had a locally advanced thyroid cancer with a tracheal invasion. With a maximal follow-up of 2 years and 7 months, there was no complication related to surgery and no recurrence of thyroid cancer. De novo generation of cartilage within the aortic matrices allowed stent removal in both patients. Since the JAMA publication, a new prospective observational study using the same methodology has restarted on March 2019. Of the 7 new patients included, 2 had recurrent or extended thyroid cancer. Thus, 4 patients with thyroid cancer and tracheal invasion received this innovative approach of airway bioengineering using a stented cryopreserved aortic allograft. The survival of differentiated thyroid cancers is directly conditioned by a complete surgical resection and the absence of residual cancer or recurrence in the tracheal and/or esophageal wall. Locally invasive disease from differentiated thyroid cancer represents 13% to 15% of patients. T4 locally-advanced thyroid cancer includes gross extrathyroidal extension into major neck structures; T4a gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus or recurrent laryngeal nerve from a tumor of any size; T4b gross extrathyroidal extension invading prevertebral fascia or encasing carotid artery or mediastinal vessels from a tumor of any size. Papillary thyroid carcinoma represents the most common type of differentiated thyroid cancer associated with extrathyroidal spread. Invasion of local structures most commonly involves the strap muscles, recurrent laryngeal nerve, and trachea. Extrathyroidal spread may also affect the larynx, esophagus, and major vessels, although this is rare. Finally, 50% of all deaths are due to tracheal invasion that is poorly managed or not treated early. The incidence of these invasions is probably underestimated, reaching between 1 and 20% of patients operated for a differentiated cancer of the thyroid. Only radical surgery can improve the prognosis. No other current treatment (radiotherapy, chemotherapy) can be considered as curative. There is no recommendation for the treatment of these invasions (abstention, shaving, tracheal resection with direct anastomosis, pharyngo-laryngectomy) and therapeutic decisions are left to the discretion of the teams and their medical/surgical expertise. This study propose to evaluate the use of an innovative approach in patients with locally advanced thyroid cancer to provide a R0 surgical resection and then a better prognosis. The use of this approach could be proposed in case of incomplete resection after thyroidectomy, redo surgery, recurrence especially if there is a vocal cord paralysis and extensive tracheal invasion. This is the first known study proposing to evaluate a new approach for patients with extended thyroid cancer invading the trachea. In fact, this group of patients is usually referred to a palliative treatment including local therapy, radiotherapy and more rarely chemotherapy.

Conditions

Differentiated Thyroid Cancer

Keywords

differentiated thyroid cancer; Tracheal replacement; aortic allograft supported by a silicone stent; cryopreserved aortic allograft

Outcome Measures

Primary Outcomes (1)

• SAFETY / TOLERABILITY / EFFICACY

  local recurrence-free survival

  Throughout the follow-up period of a minimum of 12 months and a maximum of 36 months.

Secondary Outcomes (4)

• SAFETY / TOLERABILITY / EFFICACY

  During minimum 12 months and maximum 36 months.

• SAFETY / TOLERABILITY / EFFICACY

  minimum 12 months and maximum 36 months

• SAFETY / TOLERABILITY / EFFICACY

  Before treatment initiation, and at 6 and 12 months

• SAFETY / TOLERABILITY / EFFICACY

  POST-OPERATIVE (from M0 to M1)

Study Arms (2)

Surgery

EXPERIMENTAL

Surgical resection using the innovative approach

Procedure: Tracheal replacement using a cryopreserved aortic allograft for R0 resection in locally advanced thyroid cancer

Conventional treatment

ACTIVE COMPARATOR

radioactive iodine treatment +/- external beam radiotherapy +/- tyrosine kinase inhibitor, based on multidisciplinary team (MDT) decisions

Other: Conventional treatment

Interventions

Tracheal replacement using a cryopreserved aortic allograft for R0 resection in locally advanced thyroid cancer PROCEDURE

Resection and replacement of the invaded tracheal segment with a cryopreserved aortic allograft supported by a silicone tracheal prosthesis (in the surgery arm).

Surgery

Conventional treatment OTHER

radiotherapy and/or medical treatment

Conventional treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with thyroid cancer involving the trachea and/or cricoid cartilage that is not amenable to simple resection-anastomosis, regardless of prior treatment status;
• patients with any histological type of thyroid cancer, excluding the undifferentiated/anaplastic type;
• patients deemed eligible for surgical resection based on standard preoperative assessment;
• lesions considered unresectable via standard procedures;
• women using effective contraception throughout the study duration, in accordance with CTCG recommendations.

You may not qualify if:

• age under 18 years;
• patients unable to provide consent;
• patients not covered by the French Social Security system;
• patients with undifferentiated/anaplastic thyroid cancer;
• patients for whom standard preoperative assessment precludes surgical resection (e.g., severe malnutrition, limiting cardiovascular disease, limiting respiratory disease with DLCO \< 35% or VO2max \< 10 ml/min/kg);
• patients with \*de novo\* thyroid cancer and minimal tracheal invasion suitable for simple resection-anastomosis;
• patients with \*RET\* mutations;
• pregnant or breastfeeding women;
• patients participating in another interventional study;

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Avicenne

Bobigny, Île-de-France Region, 93009 Bobigny Cedex, France

Location

Related Publications (1)

• 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.

  PMID: 29800033 BACKGROUND

Central Study Contacts

Emmanuel MARTINOD, Pr

CONTACT

+33148955231, +33689785327; emmanuel.martinod@aphp.fr

Christophe TRESSALLET, Pr

CONTACT

+33148955231

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two parallel groups: Group 1: surgical group involving resection and replacement of the invaded tracheal segment with a cryopreserved aortic allograft supported by a silicone tracheal prosthesis; Group 2 : conventional treatment group (radiotherapy and/or medical treatment) recommended during a multidisciplinary team meeting.

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 16, 2026
• Study Start (Estimated): July 27, 2027
• Primary Completion (Estimated): August 27, 2030
• Study Completion (Estimated): August 27, 2030
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)