NCT07010393

Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study

A Multicenter Prospective-Retrospective Real-World Study Evaluating Conversion-to-Surgery and Survival After Genotype-Matched Neoadjuvant Systemic Therapy in Locally Advanced Thyroid Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 335 (estimated)
• Sponsor: Fujian Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Primary 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.

Conditions

• Thyroid Neoplasms

Interventions

Type	Name	Description
DRUG	Dabrafenib	150 mg orally twice daily; ≤4 × 28-day cycles
DRUG	Trametinib	2 mg orally once daily; same duration
DRUG	Selpercatinib	160 mg orally twice daily; ≤4 cycles
DRUG	Pralsetinib	retrospective, 400 mg orally once daily; ≤4 cycles
DRUG	Lenvatinib	24 mg orally once daily; ≤4 cycles
DRUG	Larotrectinib	Larotrectinib 100 mg orally twice daily, continuous 28-day cycles.
DRUG	Anlotinib	12 mg orally once daily; 2 weeks on / 1 week off, ≤4 cycles (alternative)
DRUG	Pembrolizumab	200 mg IV infusion every 3 weeks; ≤4 cycles
DRUG	Sintilimab	200 mg IV infusion every 3 weeks; ≤4 cycles
DRUG	Cabozantinib	Cabozantinib 60 mg orally once daily, continuous 28-day cycles.
DRUG	Bemosuzumab	China PD-L1 antibody bemosuzumab 900 mg IV every 2 weeks (14-day cycle).
PROCEDURE	Conversion Surgery	Conversion Surgery if resectable

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2025-06-08
• Last updated: 2025-06-08

Locations

1 site across 1 country: China