Tracheal Replacement Using A Cryopreserved Aortic Allograft For R0 Resection In Locally Advanced Thyroid Cancer (TRITON 02 Tracheal Replacement In ThyrOid caNcer) (TRITON 02)
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Emmanuel MARTINOD, Pr
- Phone Number: +33148955231, +33689785327
- Email: emmanuel.martinod@aphp.fr
Study Contact Backup
- Name: Christophe TRESSALLET, Pr
- Phone Number: +33148955231
Study Locations
-
-
Île-de-France Region
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Bobigny, Île-de-France Region, France, 93009 Bobigny Cedex
- Hôpital Avicenne
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Study inclusion criteria will be approved by a multidisciplinary tumor board (local or national, e.g., TUTHYREF, if necessary) and will include the following:
- 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.
Exclusion Criteria:
- 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;
- patients under legal guardianship or trusteeship. Note that for patients with metastatic disease, the decision regarding inclusion or exclusion will be made on a case-by-case basis during the multidisciplinary team (MDT) meeting; contraindications to standardized tracheal resection and primary anastomosis reconstruction will be determined by the MDT; and all histological types-including medullary carcinoma-will be included, with the exception of undifferentiated/anaplastic types, to ensure a homogeneous group regarding local invasion and prognosis. Note also that minimal invasion (<2 cm)-in the absence of repeat surgery, and regardless of the presence or absence of recurrent laryngeal nerve paralysis-requires resection-anastomosis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Surgery
Surgical resection using the innovative approach
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Resection and replacement of the invaded tracheal segment with a cryopreserved aortic allograft supported by a silicone tracheal prosthesis (in the surgery arm).
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Active Comparator: Conventional treatment
radioactive iodine treatment +/- external beam radiotherapy +/- tyrosine kinase inhibitor, based on multidisciplinary team (MDT) decisions
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radiotherapy and/or medical treatment
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
SAFETY / TOLERABILITY / EFFICACY
Time Frame: Throughout the follow-up period of a minimum of 12 months and a maximum of 36 months.
|
local recurrence-free survival
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Throughout the follow-up period of a minimum of 12 months and a maximum of 36 months.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
SAFETY / TOLERABILITY / EFFICACY
Time Frame: During minimum 12 months and maximum 36 months.
|
- Overall mortality during the follow-up period (minimum 12 months, maximum 36 months).
|
During minimum 12 months and maximum 36 months.
|
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SAFETY / TOLERABILITY / EFFICACY
Time Frame: minimum 12 months and maximum 36 months
|
Rates of in-hospital and late postoperative complications during the follow-up period (minimum 12 months, maximum 36 months).
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minimum 12 months and maximum 36 months
|
|
SAFETY / TOLERABILITY / EFFICACY
Time Frame: Before treatment initiation, and at 6 and 12 months
|
Quality of life assessed using the St George's questionnaire (before treatment initiation, and at 6 and 12 months).
|
Before treatment initiation, and at 6 and 12 months
|
|
SAFETY / TOLERABILITY / EFFICACY
Time Frame: POST-OPERATIVE (from M0 to M1)
|
R0 resection status (assessed postoperatively based on the pathological findings of the resected specimen) will be evaluated for patients in the surgical arm.
|
POST-OPERATIVE (from M0 to M1)
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- APHP200131
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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