Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Thyroid Neoplasms | Thyroid Gland Neoplasm | ALIAS | 0.90 |
Interventions
Interventions (12)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Anlotinib | Drug | — | UNRESOLVED |
| Bemosuzumab | Drug | — | UNRESOLVED |
| Cabozantinib | Drug | Cabozantinib | ALIAS |
| Conversion Surgery | Procedure | — | UNRESOLVED |
| Dabrafenib | Drug | Dabrafenib | ALIAS |
| Larotrectinib | Drug | Larotrectinib | ALIAS |
| Lenvatinib | Drug | Lenvatinib | ALIAS |
| Pembrolizumab | Drug | Pembrolizumab | ALIAS |
| Pralsetinib | Drug |
Design
Arms and outcomes
Arms (7)
- 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
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria:
1. Age ≥ 18 years at enrollment.
2. Histologically or cytologically confirmed thyroid carcinoma that meets ≥ 1 of the following:
* Radioactive-iodine-refractory differentiated thyroid carcinoma (DTC)
* Medullary thyroid carcinoma (MTC)
* Anaplastic or poorly differentiated thyroid carcinoma (ATC/PDTC)
* Other locally advanced / metastatic thyroid malignancy deemed incurable by surgery alone.
3. Disease judged unresectable or entailing prohibitively high-morbidity surgery at baseline by a multidisciplinary thyroid-oncology board.
4. Documented molecular or immunophenotype qualifying for ≥ 1 study arm:
* BRAF V600E mutation
* RET gene fusion
* RET activating point mutation (e.g., M918T)
* NTRK1/2/3 fusion
* Isolated TERT-promoter mutation with no BRAF/RET/NTRK alterations
* Driver-negative / VEGFR-wild type ("triple-negative")
* PD-L1 expression ≥ 1 % OR progression after prior multi-kinase inhibitor (MKI).
5. ECOG Performance Status 0-2.
6. At least one measurable lesion per RECIST v1.1 / iRECIST (MTC with calcitonin/CEA evaluable disease accepted).
7. Written informed consent obtained.
Exclusion Criteria:
1. Untreated or symptomatic CNS metastases; patients with treated, stable lesions ≥ 4 weeks and off corticosteroids are eligible.
2. 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).References
Publications (0)
Data not yet available