Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-31 @ 11:12 AM
Study NCT ID:
NCT07419932
Status:
RECRUITING
Last Update Posted:
2026-02-19
First Post:
2026-02-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D013964', 'term': 'Thyroid Neoplasms'}], 'ancestors': [{'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D013959', 'term': 'Thyroid Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C531958', 'term': 'lenvatinib'}, {'id': 'C000625192', 'term': 'anlotinib'}, {'id': 'C561627', 'term': 'dabrafenib'}, {'id': 'C560077', 'term': 'trametinib'}, {'id': 'C000656166', 'term': 'selpercatinib'}, {'id': 'C000655704', 'term': 'pralsetinib'}, {'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'D000077594', 'term': 'Nivolumab'}, {'id': 'D001706', 'term': 'Biopsy'}, {'id': 'D062005', 'term': 'Biopsy, Large-Core Needle'}, {'id': 'D044963', 'term': 'Biopsy, Fine-Needle'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D003581', 'term': 'Cytodiagnosis'}, {'id': 'D003584', 'term': 'Cytological Techniques'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D003949', 'term': 'Diagnostic Techniques, Surgical'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D001707', 'term': 'Biopsy, Needle'}, {'id': 'D011677', 'term': 'Punctures'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Fresh tumor specimens will be prospectively collected from patients with locally advanced thyroid cancer (LATC) enrolled in this study after written informed consent is obtained. These specimens include tumor tissue obtained by core needle biopsy prior to neoadjuvant therapy, as well as matched fresh tumor tissue and adjacent non-tumor tissue collected during subsequent surgical resection.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 120}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-12-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2029-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-12', 'studyFirstSubmitDate': '2026-02-06', 'studyFirstSubmitQcDate': '2026-02-12', 'lastUpdatePostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Tumor Microenvironment and Immune Profiling', 'timeFrame': 'From baseline (pre-neoadjuvant therapy biopsy) to surgery.', 'description': 'Changes in tumor immune cell composition following neoadjuvant therapy, assessed by single-cell RNA sequencing of tumor tissue obtained at baseline (pre-neoadjuvant biopsy) and at surgery. The outcome measure will be the change in the proportion of major immune cell subsets within the tumor microenvironment.'}], 'primaryOutcomes': [{'measure': 'Radiographic Response', 'timeFrame': 'From baseline to preoperative imaging assessment after neoadjuvant therapy.', 'description': 'Radiographic response of tumors and lymph nodes to neoadjuvant treatment will be assessed using contrast-enhanced computed tomography (CT) and defined by RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions. Partial response (PR) is defined as ≥30% decrease in the sum of the longest diameter of target lesion; progressive disease (PD) as ≥20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is defined as \\<20% increase and \\<30% decrease in the sum of the longest diameter of target lesions. The objective response rate (ORR) will be calculated as the proportion of patients achieving CR or PR.'}, {'measure': 'Pathologic Response', 'timeFrame': 'At the time of surgery, based on postoperative pathological evaluation.', 'description': 'Pathologic response in resected tumors and lymph nodes will be assessed on hematoxylin and eosin (H\\&E)-stained slides of the entire tumor bed and all sampled lymph nodes. All slides will be digitally scanned and independently reviewed by two pathologists. Pathological complete response (pCR) is defined as the absence of viable tumor cells in all examined slides. For this study, pathological partial response (pPR) is defined as \\<50% viable residual tumor, and pathological non-response (pNR) as ≥50% viable residual tumor in the resected specimen.'}, {'measure': 'Progression-Free Survival (PFS)', 'timeFrame': 'From the date of surgery until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.', 'description': 'Time from surgery to the earliest date of disease progression or all-cause death.'}], 'secondaryOutcomes': [{'measure': 'Biochemical Response', 'timeFrame': 'From 4 weeks to 12 months after surgery.', 'description': 'Serum thyroglobulin (Tg) levels in patients with DTC and serum calcitonin and carcinoembryonic antigen (CEA) levels in patients with MTC will be measured after definitive surgery. Levels will be:\n\n1. compared across subgroups defined by radiographic response (per RECIST v1.1) and pathologic response (e.g., pCR, pPR, pNR) within the neoadjuvant therapy cohort; and\n2. compared between the neoadjuvant therapy plus surgery group and the upfront surgery group at matched postoperative timepoints.'}, {'measure': 'R0/1 Resection Rate', 'timeFrame': 'At the time of surgery.', 'description': 'Percentage of resected participants with no residual tumor (R0) or microscopic residual tumor (R1) on final pathology.'}, {'measure': 'Change in Surgical Complexity and Morbidity Score', 'timeFrame': 'From baseline to preoperative imaging assessment after neoadjuvant therapy.', 'description': 'The MGH/MEE-MSK-MD Anderson Surgical Morbidity Complexity Score (SMCS) will be used to assess surgical complexity. The SCMS is a validated 5-level scale \\[mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)\\] that quantifies surgical complexity based on preoperative radiographic assessment of tumor involvement with critical neck structures.、 The SMCS will be collected at enrollment (baseline imaging) and prior to surgery using restaging imaging. The change in SCMS will be reported as the median SCMS value.'}, {'measure': 'Surgery Related Adverse Events', 'timeFrame': 'During surgery or within 30 days after surgery.', 'description': 'Surgery related adverse events (SRAEs) are defined as complications occurring during surgery or within 30 days postoperatively. Postoperative complications will be documented and classified according to the Clavien-Dindo grading system, including but not limited to hemorrhage, hypoparathyroidism, vocal cord palsy, chyle leakage, and wound infection.'}, {'measure': 'Incidence of Grade ≥ 3 Neoadjuvant Treatment-Related Advert Events', 'timeFrame': 'From baseline to 30 days after the last dose of neoadjuvant therapy.', 'description': 'Number and percentage of participants experiencing Grade 3 or higher adverse events, assessed according to CTCAE v5.0.'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'From the date of surgery to death from any cause, assessed up to 24 months.', 'description': 'Time from surgery to all-cause death, with survivors censored at the date of last follow-up.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Thyroid Cancer', 'locally advanced', 'Neoadjuvant Therapy'], 'conditions': ['Thyroid Cancer', 'Thyroid Neoplasms']}, 'descriptionModule': {'briefSummary': 'This multicenter observational study aims to evaluate the safety and efficacy of neoadjuvant therapy in patients with locally advanced thyroid cancer, focusing on imaging, biochemical, and pathological responses, as well as short-term surgical outcomes and long-term prognosis.', 'detailedDescription': 'Locally advanced thyroid cancer (LATC) is characterized by tumors that extensively invade critical adjacent structures, leading to a poor prognosis and significantly contributing to thyroid cancer-related mortality. In recent years, neoadjuvant therapy has been increasingly applied to LATC, resulting in tumor downstaging and improved resectability in some patients. However, challenges remain in optimizing radical treatment strategies and improving long-term outcomes for LATC patients.\n\nThis study aims to systematically analyze the clinical data of LATC patients who underwent neoadjuvant treatment followed by radical thyroidectomy, with a focus on the following objectives: (1) to summarize the imaging, biochemical, and pathological responses to neoadjuvant therapy and investigate associated recurrence risk stratification; (2) to evaluate the short-term efficacy of surgical outcomes (e.g., R0/R1 resection rates, perioperative complications) and long-term prognosis (e.g., survival outcomes), with comparisons to a control cohort of patients undergoing upfront surgery.\n\nFurthermore, the investigators will examine changes in the profiles and functions of immune cells within tumors, lymph nodes, and peripheral blood after the interventions, and assess their correlation with neoadjuvant response and prognosis. Additionally, based on multi-omics features, including pathological histology, ultrasonomics, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics, the study aims to identify potential biological markers for tumor resistance mechanisms and explore biomarkers that could inform clinical decision-making.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '14 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients diagnosed with LATC may be managed with either neoadjuvant therapy followed by surgery or upfront surgery, depending on resectability and multidisciplinary team assessment.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 14 years at enrollment.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Histologically or cytologically confirmed thyroid carcinoma, including differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC).\n* LATC defined as clinical stage T4N0-1 at baseline, as confirmed by a multidisciplinary thyroid oncology board.\n* For patients with distant metastasis, the potential benefit from surgical intervention must be documented by the treating team.\n* Presence of at least one measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.\n* Normal function of major organs.\n* Written informed consent obtained.\n\nExclusion Criteria:\n\n* Patients who refuse tumor tissue biopsy or surgery.\n* Prior thyroid or major neck surgery.\n* History of other treatments for cancer, including surgery, chemotherapy, radiotherapy, or molecular targeted therapy, that may affect the current treatment plan.\n* Concurrent active malignancies.\n* Uncontrolled systemic diseases, including diabetes, hypertension, etc.\n* Pregnancy or breastfeeding.'}, 'identificationModule': {'nctId': 'NCT07419932', 'acronym': 'NeoLATC', 'briefTitle': 'Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Fujian Medical University'}, 'officialTitle': 'Biochemical, Radiological and Pathological Responses to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer: A Multicenter Study', 'orgStudyIdInfo': {'id': 'FMUUH-LACTCS002'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Neoadjuvant Treatment Group', 'description': 'Participants will undergo neoadjuvant treatment with multikinase inhibitors (mTKIs), specific receptor inhibitors (including RET inhibitors or BRAF ± MEK inhibitors), or combination regimens containing a PD-1 inhibitor. All regimens will be administered for at least two cycles prior to surgery.', 'interventionNames': ['Drug: Multitarget Tyrosine Kinase Inhibitors', 'Drug: BRAF inhibitor dabrafenib and MEK inhibitor trametinib', 'Drug: RET Inhibitor', 'Drug: PD(L)-1 inhibitor', 'Procedure: Biopsy', 'Procedure: Surgery']}, {'label': 'Upfront Surgery Group', 'description': "The participants in this group will undergo radical surgery directly after the diagnosis of LATC, based on MDT consensus and patient's preference.", 'interventionNames': ['Procedure: Biopsy', 'Procedure: Surgery']}], 'interventions': [{'name': 'Multitarget Tyrosine Kinase Inhibitors', 'type': 'DRUG', 'otherNames': ['Lenvatinib', 'Anlotinib'], 'description': 'Patients with or without actionable genomic alterations may receive a multikinase inhibitor (e.g., lenvatinib or anlotinib) as neoadjuvant therapy.', 'armGroupLabels': ['Neoadjuvant Treatment Group']}, {'name': 'BRAF inhibitor dabrafenib and MEK inhibitor trametinib', 'type': 'DRUG', 'otherNames': ['Dabrafenib', 'Trametinib'], 'description': 'Patients with BRAF V600E mutation may receive combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib.', 'armGroupLabels': ['Neoadjuvant Treatment Group']}, {'name': 'RET Inhibitor', 'type': 'DRUG', 'otherNames': ['Selpercatinib', 'Pralsetinib'], 'description': 'Patients with RET fusion may receive a selective RET inhibitor (e.g., selpercatinib).', 'armGroupLabels': ['Neoadjuvant Treatment Group']}, {'name': 'PD(L)-1 inhibitor', 'type': 'DRUG', 'otherNames': ['Pembrolizumab', 'Nivolumab'], 'description': 'In selected cases, combination regimens incorporating immunotherapy may be considered.', 'armGroupLabels': ['Neoadjuvant Treatment Group']}, {'name': 'Biopsy', 'type': 'PROCEDURE', 'otherNames': ['Core Needle Biopsy', 'Fine-needle Aspiration'], 'description': 'While fine-needle aspiration (FNA) is the standard initial diagnostic modality for thyroid nodules, core needle biopsy (CNB) is performed to obtain tissue cores for histological subtyping and molecular profiling in locally advanced cases.', 'armGroupLabels': ['Neoadjuvant Treatment Group', 'Upfront Surgery Group']}, {'name': 'Surgery', 'type': 'PROCEDURE', 'description': 'Patients considered resectable after neoadjuvant therapy will undergo definitive surgery, as determined by consensus of the multidisciplinary team (MDT).', 'armGroupLabels': ['Neoadjuvant Treatment Group']}, {'name': 'Surgery', 'type': 'PROCEDURE', 'description': 'Patients deemed resectable at baseline will undergo immediate surgery based on MDT consensus and informed patient preference.', 'armGroupLabels': ['Upfront Surgery Group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '350001', 'city': 'Fuzhou', 'state': 'Fujian', 'status': 'RECRUITING', 'country': 'China', 'contacts': [{'name': 'Wenxin Zhao, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'fzhzwx6688@163.com', 'phone': '+86-591-86218065'}], 'facility': 'Fujian Medical University Union Hospital', 'geoPoint': {'lat': 26.06139, 'lon': 119.30611}}], 'centralContacts': [{'name': 'Wenxin Zhao, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'fzhzwx6688@163.com', 'phone': '+86-591-86218065'}, {'name': 'Zihan Tang, M.D.', 'role': 'CONTACT', 'email': 'tzhan2016@163.com', 'phone': '+86-13615083322'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fujian Medical University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor and Chief Surgeon, Department of Thyroid Surgery', 'investigatorFullName': 'wenxin zhao', 'investigatorAffiliation': 'Fujian Medical University Union Hospital'}}}}