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

Sponsor
Fujian Medical University
Study ID
NCT07010393
Phase
PHASE4
Status
Not Yet Recruiting

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Conditions

  • Thyroid Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Jul 1, 2025
Status verified
Jan 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2028

Study Design

Enrollment
335 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: BRAF V600E Mutation
    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.
  • Experimental: RET Fusion PTC
    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.
  • Experimental: RET Point-Mutation MTC
    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.
  • Experimental: NTRK Fusion
    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.
  • Experimental: TERT-Only (MKI)
    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.
  • Experimental: Triple-Negative (driver-negative) - MKI
    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.
  • Experimental: PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKI
    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.

Primary Outcome Measure

Real-World Progression-Free Survival (rwPFS) [ Time Frame: Baseline to radiologic/clinical progression or death, whichever occurs first, up to 36 months ]

Central Contacts

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