Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
Background:
- Medullary thyroid carcinoma (MTC) is common in people with a genetic disorder called multiple endocrine neoplasia (MEN).
- Vandetanib is an experimental drug that blocks a defective protein receptor (rearranged during transfection (RET) receptor) found on the surface of cancer cells in people with MEN. It is thought that this protein is a primary cause of MTC in people with MEN.
Objectives:
- To study the activity of Vandetanib in children and adolescents with MEN-related MTC by measuring the change in tumor size, in blood levels of proteins produced the tumor (calcitonin and carcinoembryonic antigen (CEA) and in tumor-related diarrhea.
- To determine the safety and tolerability of Vandetanib in children and adolescents.
- To study how the body handles Vandetanib in children and adolescents.
- To determine the effect of Vandetanib on the survival of children and adolescents with MTC.
Eligibility:
-Children and adolescents 5 to 18 years of age with MTC whose tumor cannot be surgically removed or has grown back after treatment or has metastasized (spread beyond the thyroid gland).
Design:
- Patients take Vandetanib once a day in 28-day cycles. The first patients enrolled in the study are started on a low dose of Vandetanib to determine tolerability.
- Patients have periodic blood tests, electrocardiograms, and blood pressure measurements to look for side effects of Vandetanib.
- Blood tests and imaging scans (magnetic resonance imaging (MRI), computed tomography (CT), bone and octreoscan) are done every 8 weeks for the first 32 weeks of treatment and then every 16 weeks for the duration of the treatment period.
- Patients who have tumor-related diarrhea keep a daily record of the number and consistency of bowel movements.
详细描述
BACKGROUND:
Hereditary medullary thyroid carcinoma (MTC), which is a rare calcitonin-producing tumor arising from the parafollicular C cells of the thyroid, is often a manifestation of multiple endocrine neoplasia (MEN) types 2A and 2B and can be detected in children as young as five years in MEN 2A and one year in those with MEN 2B
MEN results from an activating mutation in the rearranged during transfection (RET) proto-oncogene resulting in a constitutively activated receptor tyrosine kinase (RTK)
Vandetanib is an orally bioavailable multi-RTK inhibitor that blocks the mutant RET gene product and has anti-tumor activity in adults with hereditary MTC
OBJECTIVES:
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
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Vandetanib
Vandetanib administered as a once daily dose, continuously (1 cycle = 28 days) at a dose of 150 mg/m^2/day.
干预措施: Vandetanib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: During Cycle 1 and Cycle 2, approximately 56 days
The MTD is the highest dose of Vandetanib tolerated at which a participant experienced a dose limiting toxicity (DLT) during the first two cycles of drug.
Overall Percentage of Participants With an Objective Response Defined as a Complete Response (CR) or Partial Response (PR)
时间窗: Patients were evaluated for response after every 2 cycles x 4 (prior to cycles 1, 3, 5, 7, and 9) and then after every 4 cycles X 1 (prior to cycle 13) and then every 6 cycles (prior to cycle 19, 25, 31, etc). Response was followed for an median of 59 mon
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive Disease is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Number of Participants With an Increase or Decrease in Carcinoembryonic Antigen (CEA) Biomarker Response(Every 2 cycles x 4 (prior to cycles 1, 3, 5, 7 and 9), prior to cycle 13, and then every 6 cycles (prior to cycle 19, 25, 31, etc). Patients were followed for response for a median of 59 months.)
- Percent Change in Calcitonin (CTN) Biomarker Response After Cycle 1(Cycle 1 (28 days))
- Area Under the Concentration Time Curve (AUC 0-24h)(Cycle 1, Pre-dose and then 1, 2, 4, 6, 8, 10 and 24 hour post dose.)
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0)(Date treatment consent signed to date off study, approximately 142 months and 8 days.)
研究者
Brigitte Widemann, M.D.
Principal Investigator
National Cancer Institute (NCI)