Lenvatinib in Patients With Advanced Parathyroid Carcinoma (ALPS)

Inclusion Criteria

Participants must meet all of the following inclusion criteria prior to enrollment in the clinical trial:

1. Parathyroid carcinoma confirmed by histopathological or cytological examination.

2. Unresectable advanced or metastatic disease:

   1. Primary or locally recurrent lesions that extensively involve major blood vessels, the airway, or other critical organs, making curative surgical resection infeasible.
   2. Presence of multiple distant metastases (e.g., lung, liver, or bone) that preclude curative surgical resection.
   3. Additional curative surgical resection considered difficult due to repeated disease recurrence.
   4. Curative surgical resection considered inappropriate by the investigator due to the participant's general condition, comorbidities, or other clinical considerations.

3. At least one measurable lesion according to RECIST version 1.1.

4. Age ≥19 years at the time of informed consent.

5. ECOG performance status of 0 or 1.

6. Adequate organ and bone marrow function, as demonstrated by all of the following screening laboratory criteria:

   1. Absolute neutrophil count (ANC) ≥1,500/mm³.
   2. Platelet count ≥100,000/mm³.
   3. Hemoglobin ≥9 g/dL.
   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × the upper limit of normal (ULN); ≤5 × ULN in participants with liver metastases.
   5. Total bilirubin ≤1.5 × ULN; ≤3 mg/dL is permitted in participants with Gilbert syndrome.
   6. Serum creatinine ≤2.5 × ULN or estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², calculated using the CKD-EPI equation.
   7. Urine protein-to-creatinine ratio (UPCR) ≤1 mg/mg or 24-hour urine protein <1 g.

7. Participants who understand the purpose and procedures of the clinical trial and voluntarily provide written informed consent.

8. Sexually active participants of childbearing potential and their partners who agree to use adequate contraception (e.g., male or female condoms).

9. Female participants of childbearing potential must have a negative pregnancy test at screening. Women who have had menstruation within the preceding 12 months will be considered to be of childbearing potential. Amenorrhea due to anticancer treatment, hormonal suppression, low body weight, or other causes may also be considered consistent with childbearing potential.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded from participation in the study:

1. Prior treatment with lenvatinib for advanced or metastatic parathyroid carcinoma.

2. Treatment with another investigational medicinal product within 14 days before the first administration of the study drug.

3. Radiation therapy for bone metastases within 7 days before initiation of study treatment, or other external beam radiation therapy within 14 days before initiation of study treatment.

4. Active brain metastases. However, untreated asymptomatic and stable brain metastases, or brain metastases that have been adequately treated with radiation therapy or surgery (e.g., radiosurgery), are permitted if the brain metastases have remained stable for at least 14 days before initiation of study treatment and no neurological symptoms are present at enrollment.

5. Uncontrolled or clinically significant comorbidities, including any of the following:

   1. Clinically significant cardiovascular disease occurring within 6 months before initiation of study treatment:

      • Symptomatic congestive heart failure, unstable angina, or severe arrhythmia.
      • Uncontrolled hypertension despite appropriate treatment, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg.
      • Clinically significant and unresolved stroke, myocardial infarction, other ischemic events, or thromboembolic events (e.g., deep vein thrombosis or pulmonary embolism) occurring within 3 months before initiation of study treatment.

   2. Gastrointestinal disease or conditions associated with an increased risk of gastrointestinal perforation or fistula:

      • Gastrointestinal tumor invasion, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.
      • Pancreatic or biliary duct obstruction, or gastric outlet obstruction.
      • Intra-abdominal fistula, gastrointestinal perforation, intestinal obstruction, or intra-abdominal abscess occurring within 6 months before initiation of study treatment. Participants with completely resolved conditions may be eligible.

   3. Gross hematuria, hematemesis, or hemoptysis of ≥0.5 teaspoon (approximately 2.5 mL) within 3 months before initiation of study treatment, or a history of other significant bleeding (e.g., pulmonary hemorrhage).

   4. Radiographic evidence of cavitary pulmonary lesions or endobronchial lesions.

   5. Lesions involving major pulmonary blood vessels.

   6. Other clinically significant medical conditions, including:

      • Active infection requiring systemic treatment, HIV infection, or AIDS-related illness. Participants with hepatitis B virus (HBV) infection that is stable during or after antiviral treatment, or participants with hepatitis C virus (HCV) infection may be eligible.
      • Clinically significant unhealed wounds, ulcers, or fractures.
      • Malabsorption syndrome.
      • Moderate or severe hepatic impairment corresponding to Child-Pugh class B or C.
      • History of organ transplantation.

6. Major surgery (e.g., gastrointestinal surgery) within 28 days before initiation of study treatment, or unresolved complications from previous surgery.

7. Corrected QT interval using the Fridericia formula (QTcF) >500 msec.

8. Women who are pregnant or breastfeeding.

9. Inability to take oral medications in tablet or capsule form.

10. History of allergy or hypersensitivity to any component of the study drug.

11. Diagnosis of another malignancy within 3 years before initiation of study treatment. Exceptions include non-melanoma skin cancer, completely resected stage I breast cancer, completely resected carcinoma in situ or non-muscle-invasive bladder cancer, cervical and/or uterine carcinoma, or T1a squamous cell carcinoma of the esophagus.