Ignite Creation Date:
2025-12-25 @ 1:18 AM
Ignite Modification Date:
2026-01-06 @ 5:43 PM
Study NCT ID:
NCT07010393
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-08
First Post:
2025-05-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, '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': 'C561627', 'term': 'dabrafenib'}, {'id': 'C560077', 'term': 'trametinib'}, {'id': 'C000656166', 'term': 'selpercatinib'}, {'id': 'C000655704', 'term': 'pralsetinib'}, {'id': 'C531958', 'term': 'lenvatinib'}, {'id': 'C000609083', 'term': 'larotrectinib'}, {'id': 'C000625192', 'term': 'anlotinib'}, {'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'C000632826', 'term': 'sintilimab'}, {'id': 'C558660', 'term': 'cabozantinib'}, {'id': 'D061887', 'term': 'Conversion to Open Surgery'}], 'ancestors': [{'id': 'D004724', 'term': 'Endoscopy'}, {'id': 'D019060', 'term': 'Minimally Invasive Surgical Procedures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Assignment is open-label, non-randomized; placement into an arm is decided before first dose by a central molecular \\& PD-L1 board reviewing NGS/PCR and IHC results. No cross-over permitted.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants are assigned to seven genotype- or immunophenotype-defined, parallel, non-overlapping arms with no planned cross-over:\n\nArm 1 (BRAF V600E) - dabrafenib + trametinib\n\nArm 2 (RET fusion) - selpercatinib\n\nArm 3 (RET point-mutation MTC) - selpercatinib or retrospective cohort on pralsetinib\n\nArm 4 (NTRK fusion) - larotrectinib\n\nArm 5 (TERT-only, driver-negative for BRAF/RET) - lenvatinib, anlotinib, or cabozantinib\n\nArm 6 (Triple-negative, no actionable driver) - investigator-choice MKI (lenvatinib, anlotinib, cabozantinib)\n\nArm 7 (PD-L1 ≥ 1 % or MKI-refractory) - PD-1/PD-L1 blockade (pembrolizumab, sintilimab, or domestic PD-L1 antibody bemosuzumab) ± MKI combination (e.g., pembrolizumab + lenvatinib) per treating physician\n\nAssignment is open-label, non-randomized; placement into an arm is decided before first dose by a central molecular \\& PD-L1 board reviewing NGS/PCR and IHC results. No cross-over permitted.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 335}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-07-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-01', 'studyFirstSubmitDate': '2025-05-28', 'studyFirstSubmitQcDate': '2025-06-01', 'lastUpdatePostDateStruct': {'date': '2025-06-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-06-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Real-World Progression-Free Survival (rwPFS)', 'timeFrame': 'Baseline to radiologic/clinical progression or death, whichever occurs first, up to 36 months', 'description': 'Time from Cycle 1 Day 1 to the earliest date of disease progression (RECIST/iRECIST) or all-cause death.'}], 'secondaryOutcomes': [{'measure': 'Real-World Objective Response Rate (rwORR)', 'timeFrame': 'Baseline to first documented response, assessed every 8-12 weeks, up to 24 months', 'description': 'Percentage of patients with complete or partial response per RECIST v1.1 (or iRECIST for immunotherapy arms) as determined by local radiology.'}, {'measure': 'Pathologic Tumor Regression ≥ 50 %', 'timeFrame': 'At surgery', 'description': 'Proportion of surgical specimens showing ≥ 50 % reduction in viable tumor area compared with baseline imaging estimate.'}, {'measure': 'R0/1 Resection Rate', 'timeFrame': 'At surgery (≈ 1-5 months after first dose)', 'description': 'Percentage of resected participants whose final pathology shows microscopically negative (R0) or close (R1 ≤ 1 mm) margins.'}, {'measure': 'Conversion-to-Surgery Rate', 'timeFrame': 'Up to 12 months from first dose', 'description': 'Proportion of enrolled participants who proceed to the intended curative-intent resection after completion of neoadjuvant therapy.'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Baseline to death from any cause, censored at 36 months', 'description': 'Time from Cycle 1 Day 1 to death; survivors censored at last known follow-up.'}, {'measure': 'Duration of Response (DoR)', 'timeFrame': 'From first documented response until progression or death, up to 36 months', 'description': 'Among responders, time between initial response and subsequent disease progression or death.'}, {'measure': 'Incidence of Grade ≥ 3 Treatment-Related AEs', 'timeFrame': 'Baseline to 30 days after last dose', 'description': 'Number and percentage of participants experiencing Grade 3 or higher adverse events per CTCAE v5.0.'}, {'measure': 'Quality-of-Life Change (EORTC QLQ-THY34)', 'timeFrame': 'Baseline, pre-surgery, and 6 months post-surgery', 'description': 'Mean change from baseline in global QoL score.'}, {'measure': 'Thyroglobulin Reduction ≥ 90 %', 'timeFrame': 'Pre-surgery (≈ 4 months)', 'description': 'Proportion of differentiated-tumor participants with ≥ 90 % decrease in serum thyroglobulin from baseline.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Locally Advanced', 'Neoadjuvant Therapy', 'Real-World Study', 'BRAF V600E', 'RET Fusion', 'VEGF-TKI', 'Immunotherapy', 'Conversion Surgery', 'R0 Resection', 'Precision Oncology', 'Real-World Evidence', 'Conversion Therapy'], 'conditions': ['Thyroid Neoplasms']}, 'descriptionModule': {'briefSummary': 'This multicenter registry tests whether genomically matched neoadjuvant therapy (1-4 cycles tailored to BRAF V600E, RET fusion/mutation, isolated TERT mutation, triple-negative BRAF/RET/TERT, or ICI ± TKI) can render locally advanced, initially unresectable-or high-morbidity-thyroid cancers operable. The primary endpoint is conversion-to-surgery; key secondaries are R0/1 margin rate and 12-month event-free survival, with propensity-score weighting correcting cohort imbalances. Findings aim to define a precision-guided neoadjuvant standard for down-staging advanced thyroid tumors.', 'detailedDescription': 'This multicenter, prospective-retrospective registry will determine whether genotype-matched neoadjuvant systemic therapy can convert locally advanced, initially unresectable or high-morbidity thyroid cancers to successful surgery. Patients receive one to four 28-day cycles of treatment chosen according to actionable genomic alterations-BRAF V600E, RET fusion, RET point mutation, isolated TERT promoter mutation, "BRT triple-negative" (wild-type for BRAF/RET/TERT), or immune-checkpoint blockade ± TKI-before reassessment by a multidisciplinary team.\n\nPrimary outcome is the conversion-to-surgery rate. Key secondary outcomes include R0/1 (margin-negative) resection rate and 12-month event-free survival, defined as absence of progression, unresectability at planned surgery, recurrence, or death. Propensity-score weighting will balance baseline differences among cohorts and permit adjusted comparisons. Results will clarify the role of targeted and immunologic agents in down-staging advanced thyroid tumors and may establish a precision-guided neoadjuvant standard of care.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age ≥ 18 years at enrollment.\n2. Histologically or cytologically confirmed thyroid carcinoma that meets ≥ 1 of the following:\n\n * Radioactive-iodine-refractory differentiated thyroid carcinoma (DTC)\n * Medullary thyroid carcinoma (MTC)\n * Anaplastic or poorly differentiated thyroid carcinoma (ATC/PDTC)\n * Other locally advanced / metastatic thyroid malignancy deemed incurable by surgery alone.\n3. Disease judged unresectable or entailing prohibitively high-morbidity surgery at baseline by a multidisciplinary thyroid-oncology board.\n4. Documented molecular or immunophenotype qualifying for ≥ 1 study arm:\n\n * BRAF V600E mutation\n * RET gene fusion\n * RET activating point mutation (e.g., M918T)\n * NTRK1/2/3 fusion\n * Isolated TERT-promoter mutation with no BRAF/RET/NTRK alterations\n * Driver-negative / VEGFR-wild type ("triple-negative")\n * PD-L1 expression ≥ 1 % OR progression after prior multi-kinase inhibitor (MKI).\n5. ECOG Performance Status 0-2.\n6. At least one measurable lesion per RECIST v1.1 / iRECIST (MTC with calcitonin/CEA evaluable disease accepted).\n7. Written informed consent obtained.\n\nExclusion Criteria:\n\n1. Untreated or symptomatic CNS metastases; patients with treated, stable lesions ≥ 4 weeks and off corticosteroids are eligible.\n2. Pregnant or breastfeeding. Women and men of child-bearing potential must agree to effective contraception during study and for ≥ 120 days after last dose (≥ 180 days for men after dabrafenib/trametinib).'}, 'identificationModule': {'nctId': 'NCT07010393', 'briefTitle': 'Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study', 'organization': {'class': 'OTHER', 'fullName': 'Fujian Medical University'}, 'officialTitle': 'A Multicenter Prospective-Retrospective Real-World Study Evaluating Conversion-to-Surgery and Survival After Genotype-Matched Neoadjuvant Systemic Therapy in Locally Advanced Thyroid Carcinoma', 'orgStudyIdInfo': {'id': 'Real-Neo'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'BRAF V600E Mutation', 'description': 'Dabrafenib 150 mg PO BID + trametinib 2 mg PO QD given in 28-day cycles (Day 1-28). After Cycle 4 (Day 112 ± 7) patients undergo imaging review; if previously unresectable disease becomes operable, conversion surgery is scheduled within 3 weeks. Those still unresectable continue treatment until progression/toxicity.', 'interventionNames': ['Drug: Dabrafenib', 'Drug: Trametinib', 'Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Cabozantinib', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'RET Fusion PTC', 'description': 'Selpercatinib 160 mg PO BID, continuous 28-day cycles. Surgery conversion assessment at Day 112 (end of Cycle 4). Resectable cases proceed to thyroidectomy ± neck dissection; others maintain therapy per label.', 'interventionNames': ['Drug: Selpercatinib', 'Drug: Pralsetinib', 'Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Cabozantinib', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'RET Point-Mutation MTC', 'description': 'Prospective cohort: selpercatinib 160 mg PO BID, 28-day cycles; Retrospective sub-cohort: historical pralsetinib 400 mg PO QD (also 28-day cycles). Cycle 4 reassessment (Day 112) for potential curative resection of residual neck disease or distant oligometastases.', 'interventionNames': ['Drug: Selpercatinib', 'Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Cabozantinib', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'NTRK Fusion', 'description': 'Larotrectinib 100 mg PO BID in continuous 28-day cycles with multidisciplinary resectability evaluation after 4 cycles (Day 112). Eligible patients undergo surgery; non-eligible continue TRK inhibitor.', 'interventionNames': ['Drug: Lenvatinib', 'Drug: Larotrectinib', 'Drug: Anlotinib', 'Drug: Cabozantinib', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'TERT-Only (MKI)', 'description': 'Investigator-selected MKI: lenvatinib 24 mg PO QD (28-day cycle), anlotinib 12 mg PO d1-14 q21d (21-day cycle; Cycle 4 ends Day 84), or cabozantinib 60 mg PO QD (28-day cycle). Conversion-surgery review: Day 112 for 28-day regimens or Day 84 for anlotinib.', 'interventionNames': ['Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Pembrolizumab', 'Drug: Sintilimab', 'Drug: Cabozantinib', 'Drug: Bemosuzumab', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'Triple-Negative (driver-negative) - MKI', 'description': 'Same MKI options/cycle lengths as Arm 5. Cycle 4 resectability check (Day 112 or Day 84 depending on drug). Successful conversions proceed to definitive surgery; others remain on systemic therapy.', 'interventionNames': ['Drug: Trametinib', 'Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Pembrolizumab', 'Drug: Sintilimab', 'Drug: Cabozantinib', 'Drug: Bemosuzumab', 'Procedure: Conversion Surgery']}, {'type': 'EXPERIMENTAL', 'label': 'PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'description': 'Checkpoint agents: pembrolizumab 200 mg IV q3w (21-day cycles), sintilimab 200 mg IV q3w (21 d), or domestic PD-L1 Ab bemosuzumab 900 mg IV q2w (14-day cycles). Combination option: lenvatinib 20 mg PO QD (28-day cycles) added at investigator discretion. Conversion assessment occurs after 4 cycles of the longest component being used (e.g., Day 84 for pembrolizumab; Day 112 if combined with 28-day MKI). Resectable patients undergo surgery; others continue or switch therapy.', 'interventionNames': ['Drug: Lenvatinib', 'Drug: Anlotinib', 'Drug: Pembrolizumab', 'Drug: Sintilimab', 'Drug: Cabozantinib', 'Drug: Bemosuzumab', 'Procedure: Conversion Surgery']}], 'interventions': [{'name': 'Dabrafenib', 'type': 'DRUG', 'description': '150 mg orally twice daily; ≤4 × 28-day cycles', 'armGroupLabels': ['BRAF V600E Mutation']}, {'name': 'Trametinib', 'type': 'DRUG', 'description': '2 mg orally once daily; same duration', 'armGroupLabels': ['BRAF V600E Mutation', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Selpercatinib', 'type': 'DRUG', 'description': '160 mg orally twice daily; ≤4 cycles', 'armGroupLabels': ['RET Fusion PTC', 'RET Point-Mutation MTC']}, {'name': 'Pralsetinib', 'type': 'DRUG', 'description': 'retrospective, 400 mg orally once daily; ≤4 cycles', 'armGroupLabels': ['RET Fusion PTC']}, {'name': 'Lenvatinib', 'type': 'DRUG', 'description': '24 mg orally once daily; ≤4 cycles', 'armGroupLabels': ['BRAF V600E Mutation', 'NTRK Fusion', 'PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'RET Fusion PTC', 'RET Point-Mutation MTC', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Larotrectinib', 'type': 'DRUG', 'description': 'Larotrectinib 100 mg orally twice daily, continuous 28-day cycles.', 'armGroupLabels': ['NTRK Fusion']}, {'name': 'Anlotinib', 'type': 'DRUG', 'description': '12 mg orally once daily; 2 weeks on / 1 week off, ≤4 cycles (alternative)', 'armGroupLabels': ['BRAF V600E Mutation', 'NTRK Fusion', 'PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'RET Fusion PTC', 'RET Point-Mutation MTC', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Pembrolizumab', 'type': 'DRUG', 'description': '200 mg IV infusion every 3 weeks; ≤4 cycles', 'armGroupLabels': ['PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Sintilimab', 'type': 'DRUG', 'description': '200 mg IV infusion every 3 weeks; ≤4 cycles', 'armGroupLabels': ['PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Cabozantinib', 'type': 'DRUG', 'description': 'Cabozantinib 60 mg orally once daily, continuous 28-day cycles.', 'armGroupLabels': ['BRAF V600E Mutation', 'NTRK Fusion', 'PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'RET Fusion PTC', 'RET Point-Mutation MTC', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Bemosuzumab', 'type': 'DRUG', 'description': 'China PD-L1 antibody bemosuzumab 900 mg IV every 2 weeks (14-day cycle).', 'armGroupLabels': ['PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}, {'name': 'Conversion Surgery', 'type': 'PROCEDURE', 'description': 'Conversion Surgery if resectable', 'armGroupLabels': ['BRAF V600E Mutation', 'NTRK Fusion', 'PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI', 'RET Fusion PTC', 'RET Point-Mutation MTC', 'TERT-Only (MKI)', 'Triple-Negative (driver-negative) - MKI']}]}, 'contactsLocationsModule': {'locations': [{'zip': '350001', 'city': 'Fuzhou', 'state': 'Fujian', 'country': 'China', 'contacts': [{'name': 'Bo Wang Porfessor, MD', 'role': 'CONTACT', 'email': 'wangbo@fjmu.edu.cn'}, {'name': 'Bo Wang MD, Principal Investigator', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Fujian Medical University Union Hospital', 'geoPoint': {'lat': 26.06139, 'lon': 119.30611}}], 'centralContacts': [{'name': 'Bo Wang Professor, MD', 'role': 'CONTACT', 'email': 'wangbo@fjmu.edu.cn', 'phone': '+13959123550'}, {'name': 'Si-si Wang, MD', 'role': 'CONTACT', 'email': 'WangSiSi@fjmu.edu.cn', 'phone': '+8618650064852'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'De-identified datasets will be available 6 months after primary publication via institutional repository upon reasonable request'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fujian Medical University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Director, Head of Thyroid Surgery, Principal Investigator, Clinical Professor', 'investigatorFullName': 'Bo Wang,MD', 'investigatorAffiliation': 'Fujian Medical University Union Hospital'}}}}