Phase II Study of Lenvatinib in Patients With Advanced Parathyroid Carcinoma(ALPS)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 18
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following inclusion criteria prior to enrollment in the clinical trial:
- •Parathyroid carcinoma confirmed by histopathological or cytological examination.
- •Unresectable advanced or metastatic disease:
- •Primary or locally recurrent lesions that extensively involve major blood vessels, the airway, or other critical organs, making curative surgical resection infeasible.
- •Presence of multiple distant metastases (e.g., lung, liver, or bone) that preclude curative surgical resection.
- •Additional curative surgical resection considered difficult due to repeated disease recurrence.
- •Curative surgical resection considered inappropriate by the investigator due to the participant's general condition, comorbidities, or other clinical considerations.
- •At least one measurable lesion according to RECIST version 1.
- •Age ≥19 years at the time of informed consent.
- •ECOG performance status of 0 or
- •Adequate organ and bone marrow function, as demonstrated by all of the following screening laboratory criteria:
- •Absolute neutrophil count (ANC) ≥1,500/mm³.
- •Platelet count ≥100,000/mm³.
- •Hemoglobin ≥9 g/dL.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × the upper limit of normal (ULN); ≤5 × ULN in participants with liver metastases.
- •Total bilirubin ≤1.5 × ULN; ≤3 mg/dL is permitted in participants with Gilbert syndrome.
- •Serum creatinine ≤2.5 × ULN or estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², calculated using the CKD-EPI equation.
- •Urine protein-to-creatinine ratio (UPCR) ≤1 mg/mg or 24-hour urine protein <1 g.
- •Participants who understand the purpose and procedures of the clinical trial and voluntarily provide written informed consent.
- •Sexually active participants of childbearing potential and their partners who agree to use adequate contraception (e.g., male or female condoms).
- •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.
排除标准
- •Participants meeting any of the following criteria will be excluded from participation in the study:
- •Prior treatment with lenvatinib for advanced or metastatic parathyroid carcinoma.
- •Treatment with another investigational medicinal product within 14 days before the first administration of the study drug.
- •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.
- •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.
- •Uncontrolled or clinically significant comorbidities, including any of the following:
- •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.
- •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.
- •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).
- •Radiographic evidence of cavitary pulmonary lesions or endobronchial lesions.
- •Lesions involving major pulmonary blood vessels.
- •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.
- •Major surgery (e.g., gastrointestinal surgery) within 28 days before initiation of study treatment, or unresolved complications from previous surgery.
- •Corrected QT interval using the Fridericia formula (QTcF) >500 msec.
- •Women who are pregnant or breastfeeding.
- •Inability to take oral medications in tablet or capsule form.
- •History of allergy or hypersensitivity to any component of the study drug.
- •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.
研究组 & 干预措施
Lenvatinib monotherapy.
Advanced or metastatic parathyroid cancer patients will receive lenvatinib monotherapy.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: End of trial(approximately 3 years)
Objective Response Rate (ORR) is defined as the percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR) at least once according to RECIST version 1.1 before evidence of disease progression. ORR will be summarized in the efficacy-evaluable population and presented with a two-sided 95% confidence interval.
次要结局
- Progression-Free Survival (PFS)(End of trial(approximately 3 years))
- Overall Survival (OS)(End of trial(approximately 3 years))
- Duration of Response (DoR)(End of trial(approximately 3 years))
- Disease Control Rate (DCR)(End of trial(approximately 3 years))
- Treatment-Emergent Adverse Events(End of trial(approximately 3 years))
研究者
Chang Gon Kim
Principal Investigator
Yonsei University