Parathyroid Carcinoma

This is a multicenter, open-label, single-arm, phase II study evaluating the efficacy and safety of lenvatinib in patients with unresectable, advanced or metastatic parathyroid carcinoma. Parathyroid carcinoma is a rare malignant tumor with limited systemic treatment options in patients with unresectable, recurrent, or metastatic disease. Excessive secretion of parathyroid hormone (PTH) and resulting hypercalcemia may cause significant morbidity and adversely affect prognosis and quality of life. Although complete surgical resection is considered the only potentially curative treatment for localized disease, no established standard systemic therapy is currently available for advanced or metastatic parathyroid carcinoma. Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. Inhibition of these signaling pathways may suppress tumor angiogenesis and tumor cell proliferation. Based on the potential role of angiogenic signaling in parathyroid carcinoma and the antitumor activity of lenvatinib demonstrated in various solid tumors, lenvatinib is being investigated as a potential treatment option for advanced or metastatic parathyroid carcinoma. A total of 18 participants will be enrolled, including consideration of potential evaluability and dropout. Eligible participants must have histologically or cytologically confirmed parathyroid carcinoma that is unresectable, advanced, or metastatic, with at least one measurable lesion according to RECIST version 1.1. Participants must be at least 19 years of age and have an ECOG performance status of 0 or 1 with adequate bone marrow, renal, and hepatic function. Lenvatinib will be administered orally once daily at a starting dose of 24 mg. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for treatment discontinuation. Dose interruption or reduction to 20 mg, 14 mg, and 10 mg once daily may be implemented for treatment-related toxicities according to the protocol and applicable local prescribing information. The primary objective is to evaluate the objective response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST version 1.1. Secondary objectives include evaluation of progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the safety and tolerability of lenvatinib. Exploratory objectives include assessment of changes in corrected serum calcium and PTH levels and exploration of associations between biochemical changes and clinical outcomes such as ORR and PFS. Tumor response will be assessed according to RECIST version 1.1. Baseline imaging will be performed within 28 days before the first dose of study treatment. Tumor assessments will be performed every 8 weeks (±7 days) through Week 48 and every 12 weeks (±14 days) thereafter. Safety assessments will include adverse events, clinical laboratory tests, vital signs, physical examinations, ECOG performance status, and electrocardiograms. The overall study period is planned for 3 years, with participant enrollment from July 1, 2026, through June 30, 2028. Each participant will be followed for up to 12 months after treatment discontinuation, or until study completion, as applicable. The study is designed to evaluate whether lenvatinib provides clinically meaningful antitumor activity and an acceptable safety profile in patients with advanced or metastatic parathyroid carcinoma, while also exploring potential changes in calcium and PTH levels as disease-related biochemical outcomes.