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

ConditionThyroid Neoplasms
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-80
SponsorFujian Medical University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years at enrollment.

Radioactive-iodine-refractory differentiated thyroid carcinoma (DTC)

Medullary thyroid carcinoma (MTC)

Anaplastic or poorly differentiated thyroid carcinoma (ATC/PDTC)

Disqualifiers

Untreated or symptomatic CNS metastases; patients with treated, stable lesions ≥ 4 weeks and off corticosteroids are eligible.

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).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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/Surgery

    Conversion Surgery if resectable

Treatment groups

335 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: BRAF V600E MutationExperimental treatment 6 interventions
Group B: RET Fusion PTCExperimental treatment 6 interventions
Group C: RET Point-Mutation MTCExperimental treatment 5 interventions
Group D: NTRK FusionExperimental treatment 5 interventions
Group E: TERT-Only (MKI)Experimental treatment 7 interventions
Group F: Triple-Negative (driver-negative) - MKIExperimental treatment 8 interventions
Group G: PD-L1 ≥ 1 % / MKI-Refractory - Immunotherapy ± MKIExperimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Real-World Progression-Free Survival (rwPFS)

Time from Cycle 1 Day 1 to the earliest date of disease progression (RECIST/iRECIST) or all-cause death.

Time frame
Baseline to radiologic/clinical progression or death, whichever occurs first, up to 36 months

Secondary outcomes

1

Real-World Objective Response Rate (rwORR)

Percentage of patients with complete or partial response per RECIST v1.1 (or iRECIST for immunotherapy arms) as determined by local radiology.

Time frame
Baseline to first documented response, assessed every 8-12 weeks, up to 24 months
2

Pathologic Tumor Regression ≥ 50 %

Proportion of surgical specimens showing ≥ 50 % reduction in viable tumor area compared with baseline imaging estimate.

Time frame
At surgery
3

R0/1 Resection Rate

Percentage of resected participants whose final pathology shows microscopically negative (R0) or close (R1 ≤ 1 mm) margins.

Time frame
At surgery (≈ 1-5 months after first dose)
4

Conversion-to-Surgery Rate

Proportion of enrolled participants who proceed to the intended curative-intent resection after completion of neoadjuvant therapy.

Time frame
Up to 12 months from first dose

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fujian Medical University

Lead sponsor

Fujian Medical University Union Hospital

Sponsor institution

Source ClinicalTrials.gov

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