NCT06959511

Zanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery

Neoadjuvant Treatment With Zanzalintinib for Advanced Thyroid Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To look at the effectiveness of zanzalintinib, followed by surgery, in treating advanced thyroid cancer. The safety of this treatment will also be studied.

Detailed description

Primary Objectives • To evaluate the efficacy of neoadjuvant zanzalintinib in DTC, non-RET-mutated MTC, and poorly differentiated thyroid cancer (PDTC) by overall objective response rate (overall ORR), defined as the proportion of participants who have a minor response (MR), partial response (PR), or complete response (CR) per RECIST. Participants with locally invasive extrathyroidal and/or extra nodal DTC, non- RET-mutated MTC or PDTC who have high surgical morbidity/complexity based on baseline radiographic assessment (as measured by Thyroid Neck Surgical Morbidity/Complexity Scoring, see Section 3.2.1), will be eligible for the study. Hypothesis: Neoadjuvant administration of zanzalintinib will result in acceptable overall ORR (MR+PR+CR rate) for participants with locoregionally advanced DTC and non-RETmutated MTC, ultimately allowing patients to safely undergo complete gross surgical tumor resection with less surgical morbidity. Secondary Objectives * To evaluate the efficacy of neoadjuvant zanzalintinib in DTC, non-RET-mutated MTC or PDTC by objective response rate (ORR) per modified neck RECIST. * To evaluate the safety profile of neoadjuvant zanzalintinib in thyroid cancer. * To evaluate the efficacy of neoadjuvant zanzalintinib on progression-free survival (PFS), including overall PFS and locoregional PFS. * To measure changes in expected and actual thyroid neck surgical morbidity/complexity scoring before and after zanzalintinib treatment. * To evaluate the efficacy of neoadjuvant zanzalintinib by surgical margin status. Exploratory Objectives * To define and measure changes of patient-reported outcomes (PROs) and quality of life (QOL) as measured by MDASI-HN and EQ-5D in participants who receive zanzalintinib treatment. * To evaluate the efficacy of neoadjuvant zanzalintinib by pathologic response. * To evaluate the efficacy of neoadjuvant zanzalintinib by PET metabolic response.

Conditions

• Neoadjuvant Treatment
• Thyroid Cancer

Interventions

Type	Name	Description
DRUG	Zanzalintinib	Given by po

Timeline

• Start date: 2025-07-22
• Primary completion: 2028-03-01
• Completion: 2030-10-01
• First posted: 2025-05-06
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study