Clinical Research Directory

Drug Repurposing in Thyroid Carcinoma: a Feasibility Trial

This is a phase Ib trial that studies personalized network pharmacology-based drug repurposing in patients with advanced thyroid cancer who have no other treatment options. The main objective is to study if it is feasible to give patients individualized drug combinations selected based on their tumor genetic profile. The secondary objective is to find out whether these treatments are safe and can help control the growth of the patient tumors or stop them from getting worse.

Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.

A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy

The objective of this study is to evaluate the effect of cabozantinib compared with placebo on progression free survival (PFS) and objective response rate (ORR) in subjects with Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) who have progressed after prior vascular endothelial growth factor receptor (VEGFR)-Targeted therapy.

Study of Cabozantinib Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer/gastroesophageal junction cancer/lower esophageal cancer (GC/GEJC/LEC), colorectal cancer (CRC), head and neck (H\&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Subjects enrolled in the SAC cohorts and SAA cohort may receive combination treatment with both cabozantinib and atezolizumab after they experience radiographic progressive disease per the Investigator per RECIST 1.1. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

Sacituzumab govitEcan in THYroid Cancers

SETHY is a prospective, multicohort, phase II, single-arm, non-randomized, non-blinded, investigator-initiated study of sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory differentiated thyroid carcinoma (DTC) or anaplastic thyroid carcinoma (ATC). The main hypothesis is that treatment with sacituzumab govitecan, a anti-Trophoblast cell surface antigen 2 (TROP-2), could be an effective treatment option for patients with either differentiated and anaplastic thyroid neoplasms because TROP-2 is highly expressed at the membrane of DTC and ATC.

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

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.

rhTSH for Radioactive Iodine Remnant Ablation in Participants With Differentiated Thyroid Cancer (DTC)

This study was conducted in patients with differentiated thyroid cancer who had undergone total/near-total thyroidectomy. After surgery patients were randomized to one of two methods of performing thyroid remnant ablation. One group of patients who took thyroid hormone medicine and were euthyroid \[i.e. their thyroid stimulating hormone (TSH) levels are normal\], and received injections of rhTSH (0.9 mg daily on two consecutive days) followed by oral radioiodine. The second group of patients did not take thyroid hormone medicine so that they were hypothyroid (i.e. their TSH levels were high), and were given oral radioiodine.

rhTSH for Radioactive Iodine Remnant Ablation in Differentiated Thyroid Cancer

This is a randomized, open, parallel controlled, multi-center clinical trial; 120 subjects were randomly assigned to the test group and the control group according to 3:1.

A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors

The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b). Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have: * a solid tumor which is metastatic or recurrent (excluding colorectal cancer) * tumor with the mutation (abnormal gene) called "BRAF V600" * received required prior treatment for cancer per cohort assigned. All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day. Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.

Gender-based Impact on Safety and Efficacy of Lenvatinib in Patients With Differentiated Thyroid Cancer

Lenvatinib is approved for the treatment of radioiodine refractory differentiated thyroid cancer. Despite gender can play a crucial role un in safety and efficacy of oncological product, little is know on gender difference in lenvatinb effacacy and safety in the context of radioiodine refractory differentiated thyroid cancer. The primary objective of the study is to assess safety and toxicity profile in male and female patients in terms of dose reduction. The secondary objectives are to assess sex and gender difference in: the number and the incidence of adverse events; response rate according to RECIST criteria 1.1; progression free survival, overall survival and duration of response.

Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.

A Prospective Study to Collect Images in Patients Treated With Iodine-131 as Part of a European Research Project in Radiation Protection.

This trial is a prospective, non-interventional, monocentric study aiming to collect standard of care imaging of patients treated with Iodine-131 for the determination of dosimetric studies. Data from this study will be collected as part of an European research project called MEDIRAD. The overall objectives of this project are to enhance the scientific bases and clinical practice of radiation protection in the medical field, and more specifically to develop and implement the tools necessary to establish the range of absorbed doses delivered to healthy organs in patients undergoing thyroid ablation and the threshold absorbed dose required for thyroid ablation. This will enable patient specific treatment planning that will minimize risk to the patient while ensuring a successful outcome and will facilitate development of a large scale epidemiological study of the effect of low absorbed doses from irradiation of normal organs with internal sources of radionuclides. Patients will be followed as part of their standard of care. Imaging (SPECT/CT (Single Photon Emission Computed Tomography-Computerized Tomography) and Whole Body scintigraphy) performed at 48 hours post Iodine-131 treatment will be collected. Measures of external gamma radiation will also be collected in the European database.

Lenvatinib in Locally Advanced Invasive Thyroid Cancer

This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC). This research study involves a study drug called lenvatinib

Nomogram for Predicting Difficult Transoral and Submental Thyroidectomy

No prior studies have stratified the difficulty of transoral and submental thyroidectomy (TOaST). The investigators aimed to investigate preoperative factors as indicators of difficult TOaSTs and to develop a predictive model accordingly.

Cabozantinib In Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer.

CABOTHYROID is a prospective, exploratory, biomarker-focused, phase II, single-arm, non-randomized, non-blinded, investigator-initiated study of cabozantinib in patients with previously treated advanced radioactive-iodine refractory

Thyroglobulin Point of Care Assay for Rapid Detection of Metastatic Differentiated Thyroid Carcinoma

Background: Despite a favorable prognosis, metastatic cervical lymph nodes (LN), are not uncommon among patients with differentiated thyroid cancer (DTC). Current guidelines recommend that a suspicious cervical LN on neck ultrasound (US) should be investigated with fine needle aspiration biopsy for cytology (FNAC) and for thyroglobulin (Tg) measurement (FNA-Tg), using saline washout of the needle content. Since Tg is a protein produced exclusively by thyroid follicular cells, a positive FNA-Tg result establishes the diagnosis of metastatic DTC. Currently, following LN biopsy, a patient must wait days to weeks to receive results, that directly impacts the treatment plan. This delay may be solved by a point of care assay of the washout Tg (POC-Tg), drawn from a suspicious cervical LN. Another potential novel usage of POC-Tg is the evaluation of suspicious LN found during neck surgery for known or suspicious DTC. Here, the POC-Tg may save the time needed for the completion of 'frozen section'. The study product: POC-Tg is a lateral flow immunoassay for Tg, able to detect within minutes Tg at concentration equal to 5 ng/mL and above (the midrange of the accepted cut-off). Methods: The multi-center validation study will include 100 patients in the FNA clinic, and 150 LN (dissected from 50-150 patients) in the operating room (OR). Each LN will be evaluated using both the formal accepted method (in the FNA clinic, the combination of FNAC and FNA-Tg; and frozen section in the OR), and the novel POC-Tg. Clinical decisions will be made according to the formal evaluation only. In a retrospective analysis, the investigators will estimate the sensitivity and specificity of the POC-Tg and the formal accepted method against the reference ('gold') standard (cytology, histology and follow-up US in the FNA clinic setting, and final histology in the OR setting).

Pembrolizumab in High-risk Thyroid Cancer

This window of opportunity trial is studying a checkpoint inhibitor agent to treat differentiated thyroid cancer in a neoadjuvant setting. A checkpoint inhibitor is a compound aimed at restoring tumor immunosurveillance. The name of this agent is pembrolizumab.

Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers

This is a multi-centre, randomised, non-inferiority, phase III study in patients with low risk differentiated thyroid cancer. Patients will be identified via oncology multidisciplinary team meetings. There will be two sources of patients in the trial, with the same histological diagnoses and prognosis (i.e. recurrence risk): * Group 1: Patients who have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC will be randomised 1:1 to undergo surveillance only OR a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy). * Group 2: Patients diagnosed with low risk DTC using cytology (Thy5) but no surgery performed will be randomised 1:1 to have either a hemi-thyroidectomy OR a single-stage total thyroidectomy. The overall aim of the trial is to determine whether hemithyroidectomy is an acceptable and cost-effective surgical procedure compared to total thyroidectomy in low risk thyroid cancer. Overall, 456 patients will be recruited to the trial. Patients will be initially be followed up post-surgery then 12 monthly for 6 years.

Empirical Radioactive Iodine Therapy in DTC

The aim of the study is assessment the efficacy of empiric RAI therapy in DTC patients with elevated thyroglobulin levels and negative iodine scintigraphy.

F-18 Tetrafluoroborate PET/CT in Differentiated Thyroid Cancer

In patients who have undergone surgery for differentiated thyroid cancer and who demonstrate elevated serum Tg and/or ATg levels during follow-up after radioactive iodine therapy, lesion detection is performed using neck ultrasonography, thorax CT, and F-18 FDG PET/CT. Diagnostic whole-body scanning with low-dose I-131 is not routinely recommended in follow-up due to its low sensitivity and specificity. F-18 TFB is a highly specific imaging agent for differentiated thyroid cancer, entering thyroid follicular epithelial cells via the sodium-iodide symporter (NIS), which is expressed on the cell surface and functions through a mechanism similar to that of I-131. As a PET radiotracer, F-18 TFB has been shown to be superior to I-131 in previous studies. The primary aim of this study is to comparatively evaluate the role of F-18 TFB PET/CT versus the standard imaging modality F-18 Fluorodeoxyglucose (FDG) PET/CT in lesion detection in patients with differentiated thyroid cancer who demonstrate elevated serum Tg and/or ATg levels during follow-up after radioactive iodine therapy. The secondary aims are to investigate the factors predicting F-18 TFB PET/CT positivity and to assess the relationship between the semi-quantitative and quantitative parameters derived from F-18 TFB PET/CT and serum thyroglobulin (Tg) and anti-thyroglobulin (ATg) levels.

Radiofrequency in Differentiated Thyroid Cancer Metastatic Lymph Node: Prospective Study of Safety and Efficacy

Radiofrequency (RF) could be technically feasible and effective in the treatment of lymph node metastases of differentiated thyroid cancer. It could constitute a minimally invasive and feasible therapeutic alternative in ambulatory, allowing a reduction of the tumoral volume sufficient to limit the symptoms even to induce a tumor remission, a normalization of the tumoral markers and a better quality of life. The aim of this study is to evaluate the anti-tumor echographic efficacy at 12 months of radiofrequency on lymph node (LN) metastasis of thyroid cancer

Thyroid Hormone Replacement After Radio Iodine: Value and Efficacy

This study will be a multicentre prospective cohort study on TH-substitution after thyroid hormone withdrawal preceding radioiodine treatment.

Iodine Uptake After a Low Iodine Diet

The goal of this clinical trial is to compare the difference in thyroid uptake of a low dose radioactive iodine (10 MBq 123-I or 37 MBq 123-I) in athyreotic patients with differentiated thyroid carcinoma before and after a low iodine diet (LID) of 7 days. The main question it aims to answer is: • What is the difference in iodine uptake before and after a LID of 7 days? Uptake of a low dose of 123-iodine will be measured in participants before and after a low iodine diet of 7 days. Researchers will compare the uptake (%) before and after the LID.

Targeted Therapy to Increase RAI Uptake in Metastatic DTC

Papillary thyroid cancer (PTC) is a common type of differentiated thyroid cancer (DTC) in children and represents the second most common cancer in adolescent females. Recently targeted drugs that block many of the genetic drivers of DTC have become available. While Investigators know that these drugs shrink DTC tumors in many cases, the impact on radioactive iodine (RAI) avidity has not been systematically studied.