Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Adenocarcinoma

Adenoma

Adenoma, Oxyphilic

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma, Papillary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Papillary Thyroid Carcinoma

Thyroid Cancer, Follicular

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Trametinib

Dabrafenib

Spartalizumab

Protein Kinase Inhibitors

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Cohort A (BRAF WT tumors): trametinib (T) 2mg by mouth daily plus PDR001 400mg IV every 4 weeks

Cohort B (BRAF Mutant, resistant to previous BRAF inhibitors): dabrafenib (D) 150 mg twice daily (OR at dose the patient previously tolerated) plus PDR001 400mg IV every 4 weeks.

2mg by mouth daily

\*If patient loses the ability to swallow while on study, trametinib may be provided as a powder in bottle for reconsititution. Trametinib, as a powder in bottle, will be mixed with sterile/purified water into an oral solution and administered PO or through enteral feeding tube

150 mg twice daily (OR at dose the patient previously tolerated)

PDR001

Alan L Ho, MD, PhD

The purpose of this study is to find out whether a drug called PDR001, combined with either trametinib or dabrafenib, is a safe and effective treatment for thyroid cancer.

PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer

Phase II Study of PDR001 in Combination With MAPK Pathway Inhibitors in Patients With Radioiodine-Refractory Thyroid Cancer

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary endpoint is to determine the overall response rate (ORR=CR+PR) as documented by RECIST v1.1 criteria within each cohort.

Memorial Sloan Kettering Cancer Center

Thyroid Carcinoma, Anaplastic

Carcinoma, Medullary

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Anaplastic Thyroid Cancer

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

All adult (18 years old and older) patients registered in EUROCRINE® database with stage IV thyroid cancer, M1, N1b, or T3b and above will be included

Lymph node dissection, as well as its surgical extension, was performed according to the surgeon's discretion. Multivisceral operations involved oesophagus, trachea and larynx.

Thyroidectomy with or without lymphadenectomy or multivisceral resection

Luca Sessa, Dr

Francesco Pennestrì, Dr

Marco Raffaelli, Prof

The main aim of the study is to evaluate peri-operative surgical characteristics, operation extent, postoperative morbidity, and outcomes in patients undergoing surgery for advanced thyroid cancer in different European centers using the EUROCRINE® database.

The incidence of thyroid cancer has risen exponentially over the last decades among developed countries. Even though this is mainly attributed to small well differentiated carcinomas (DTC) with excellent prognosis, the rates of advanced disease have also elevated. While the characteristics of advanced thyroid cancer are intuitively recognized by experienced surgeons of the field, a common definition among scientific societies is yet to be reached. The four main features of advanced cancer are locally and regionally advanced disease, distant metastasis, and recurrence. Guidelines for the optimal treatment of advanced disease are mainly included in the broader guidelines of each cancer subtype, such as the American Thyroid Association (ATA) guidelines for DTC, Medullary Thyroid Carcinoma (MTC) and most recently Anaplastic Thyroid Carcinoma (ATC). In the European setting, the European Society for Medical Oncology (ESMO) 2019 guidelines on thyroid cancer include a subsection for the management of advanced disease of each thyroid cancer type. A common limitation among published guidelines is the moderate to low level of evidence upon which the advanced disease recommendations are based; however, broad consensus has been reached regarding the paramount importance of surgery if an R0/R1 resection is achievable. Recently, new advances in targeted therapy guided by genetic alterations found in the tumor have provided new treatment options for patients; therefore, latest guidelines encourage the inclusion of patients with advanced disease in these clinical trials. Finally, neoadjuvant therapy modalities are constantly gaining ground with promising results allowing a greater portion of patients to benefit from surgery.

European Multicenter Study on Surgical Management of Advanced Thyroid Cancer

European Multicenter Study on Perioperative Management, Operative Strategy, Morbidity, and Outcomes of the Surgical Management of Advanced Thyroid Cancer: (EUROCRINE® Study Group).

Reasonable requests will be evaluated by the Eurocrine Council

Descriptive analysis of overall survival, recurrence and mortality in patients undergoing surgery for advanced thyroid cancer in European centers.

Descriptive analysis of surgical perioperative characteristics of patients undergoing surgery for advanced thyroid cancer in European centers.

Descriptive analysis of short-term clinical outcomes of patients undergoing surgery for advanced thyroid cancer in European centers in terms of RLN palsy, critical neurovascular injury and voice changes through otorhinolaryngologist and clinical post-operative evaluation

Descriptive analysis of short-term clinical outcomes of patients undergoing surgery for advanced thyroid cancer in European centers in terms of surgical complications, such as bleeding, lymphorrea tracheal or oesophageal injury (detected through clinical and/or imaging evaluation).

Descriptive analysis of short-term clinical outcomes of patients undergoing surgery for advanced thyroid cancer in European centers in terms of hypocalcemia, hypoparathormonemia (detected through clinical and/or laburatoristic evaluation).

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Endothelial Growth Factors

Mitogens

cabozantinib (60 mg) once daily orally (qd)

Tablets containing 60-mg or 20-mg cabozantinib once daily orally.

Cabozantinib

Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.

Placebo

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.

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of cabozantinib in subjects with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) after prior vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy. Cabozantinib-matched placebo will be given in the control arm to blind (mask) study treatment. Approximately 300 eligible subjects will be randomized in a 2:1 ratio to receive either cabozantinib or placebo. After the primary efficacy endpoints have been analyzed and sufficient data have been collected to adequately evaluate all study endpoints to establish, for regulatory purposes, the safety and efficacy profile of the experimental drug within this study, the study will transition to an open label Maintenance Phase.

Study treatment assignment will be unknown to the subjects, investigators, study centers, Sponsor, and any Contract Research Organization affiliated with the study other than those authorized to access treatment assignment for regulatory safety reporting and submission processes, interactive response technology (IRT) system administration, and drug supply management. Cabozantinib-matched placebo will be packaged and color-, size-, and shape-matched to be indistinguishable from cabozantinib. Individual study treatment assignment will be unblinded and information provided to the Investigators upon request for subjects with radiographic progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 confirmed by the blinded independent radiology committee (BIRC).

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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy

Time to the earlier of either radiographic progressive disease (PD) or death from any cause.

Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).

Ipsen

Exelixis

Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.

cabozantinib (60 mg) once daily orally (qd)

Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.

placebo once daily orally (qd)

Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer	NCT04544111	Thyroid Cancer Thyroid Cancer,... Papillary Thyro... Follicular Thyr... Hurthle Cell Tu... Poorly Differen... Hurthle Cell Th...	Trametinib Dabrafenib PDR001	18 Years -	Memorial Sloan Kettering Cancer Center
PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer	NCT04544111	Thyroid Cancer Thyroid Cancer,... Papillary Thyro... Follicular Thyr... Hurthle Cell Tu... Poorly Differen... Hurthle Cell Th...	Trametinib Dabrafenib PDR001	18 Years -	Memorial Sloan Kettering Cancer Center
European Multicenter Study on Surgical Management of Advanced Thyroid Cancer	NCT05796960	Thyroid Carcino... Thyroid Cancer Thyroid Neoplas... Thyroid Cancer,... Thyroid Cancer,... Thyroid Medulla... Anaplastic Thyr...	Thyroidectomy w...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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	NCT03690388	Differentiated ...	Cabozantinib Placebo	16 Years -	Exelixis

Spots Global Cancer Trial Database for thyroid cancer, follicular