Phase 2 Study of Selumetinib Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 6
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This phase II trial is studying how well selumetinib works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Ascertain the objective response rate (complete response and partial response) in patients with iodine I 131-refractory papillary thyroid cancer treated with selumetinib.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this treatment in these patients. II. Determine the pharmacokinetic profile of this treatment in these patients. III. Determine the progression-free and overall survival of these patients. IV. Assess proxy measures of treatment response (thyroglobulin and PET scan) in patients treated with selumetinib.
IV. Compare relevant laboratory correlates between responders and non-responders.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed papillary thyroid cancer or papillary thyroid cancer with follicular elements
- •No longer amenable to radioactive iodine therapy or curative surgical resection
- •Tumor is no longer iodine avid
- •Tumor did not respond to the most recent radioactive iodine treatment
- •Patient is ineligible for further radioactive iodine therapy due to medical contraindications (e.g., lung toxicity)
- •Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
- •Evidence of disease progression (objective growth of existing tumors)
- •New or enlarging measurable lesions within the past 12 months
- •If the most recent imaging study is older than 12 months, patients will still be eligible if objectively measurable disease progression is associated with clinical symptoms
- •Archival tumor tissue available for mutational analysis
- •No known brain metastases
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/µL
- •ANC ≥ 1,500/µL
- •Platelet count ≥ 100,000/µL
- •Total bilirubin normal
- •AST and ALT < 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception prior to, during, and for 4 weeks after completion of study treatment
- •Able to understand and willing to sign a written informed consent document
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib (AZD6244) or its excipient Captisol®
- •QTc interval > 450 msec or other factors that increase the risk of QT prolongation
- •Arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome), including heart failure that meets NYHA class III and IV definition
- •Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
- •Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
- •At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- •Prior treatment with tyrosine kinase inhibitors that target RET or RAF
- •Prior treatment with MEK inhibitors
- •Concurrent combination antiretroviral therapy for HIV-positive patients
- •Concurrent medication that can prolong the QT interval
- •Other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I
Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: Selumetinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 2 years
ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.
次要结局
- Median Progression-Free Survival (PFS)(Up to 2 years)
- Occurrence of Treatment Related Adverse Events(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)