An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Exelixis
- 入组人数
- 330
- 试验地点
- 49
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this research study is to evaluate the progression-free survival (PFS) with XL184 as compared with placebo (an inactive substance) in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). Subjects will be randomized to receive XL184 or placebo in a 2:1 ratio. XL184 is an investigational drug that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
The Clinical Steering Committee for this study, comprised of study doctors who specialize in medullary thyroid cancer, has provided guidance regarding the design of the study. The committee includes: Douglas Ball, MD, Barry Nelkin, PhD, Martin Schlumberger, MD and Steven Sherman, MD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •The subject has a histologically confirmed diagnosis of MTC that cannot be removed by surgery, is locally advanced, or has spread in the body.
- •The subject is at least 18 years old.
- •The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤
- •The subject has documented worsening of disease (progressive disease) at screening compared with a previous CT scan or MRI image done within 14 months of screening.
- •The subject has recovered from clinically significant adverse events (side effects) due to any other medications that were administered prior to randomization.
- •The subject has adequate organ and bone marrow function.
- •Subjects who are sexually active (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatments.
- •The subject has no other diagnosis of cancer (unless non-melanoma skin cancer, an early form of cervical cancer, or another cancer diagnosed ≥ 2 years previously) and currently has no evidence of malignancy (unless non-melanoma skin cancer or an early form of cervical cancer).
- •Female subjects of childbearing potential must have a negative pregnancy test at screening.
排除标准
- •The subject has received prior treatment for their cancer within 4 weeks of randomization (6 weeks for nitrosoureas or mitomycin C).
- •The subject has received radiation to ≥ 25 % of bone marrow.
- •The subject has received treatment with other investigational agents (unapproved therapies) within 4 weeks of randomization.
- •The subject has received treatment with XL
- •The subject has brain metastases or spinal cord compression, unless completed radiation therapy ≥ 4 weeks prior to randomization and stable without steroid and without anti-convulsant treatment for ≥ 10 days.
- •The subject has a history of clinically significant episodes of vomiting blood or a recent history of vomiting > 2.5 mL (about 1/2 teaspoon) of red blood.
- •The subject has serious illness other than cancer.
- •The subject is pregnant or breastfeeding.
- •The subject has an active infection requiring ongoing treatment.
- •The subject is incapable of understanding and complying with the protocol or unable to provide informed consent.
研究组 & 干预措施
1
干预措施: XL184 (Drug)
2
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Treatment period consisted of 4-week cycles with radiologic tumor assessment every 12 weeks from date of randomization until date of first documented PD or date of death from any cause, whichever came first, assessed up to 34 months.
The duration of Progression-Free Survival (PFS) using progression events as determined by Independent Review Committee (IRC) per mRECIST, or death due to any cause. The analysis was conducted after at least 315 subjects were randomized and at least 138 events were observed.
次要结局
- Overall Survival (OS) With XL184 Compared With Placebo(The pre-specified interim analysis of Overall Survival (OS) was assessed at 44% of required events. Includes data up to 15June2011. As of this date, the number of deaths required to conduct the primary analysis had not been reached.)
- Objective Response Rate (ORR)(Assessed at the same time as primary analysis of Progression Free Survival (PFS) data. Assessed at baseline and every 12 weeks until Progressive Disease (PD) up to 34 months.)
- Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined(From time of first documentation of Objective Response (OR), confirmed at a later visit ≥28 days later as Progressive Disease (PD) as defined by mRECIST or death due to any cause, assessed up to 34 months.)
- Biochemical Response Carcinoembryonic Antigen (CEA) %(Serum tumor markers CEA evaluated from blood samples collected at screening and every 12 weeks (± 5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months.)
- Biochemical Response Calcitonin (CTN) %(Serum tumor markers CTN evaluated from blood samples collected at screening and every 12 weeks (±5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months.)