A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care for Subjects With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Whose Disease Has Progressed Despite Prior Treatment With at Least Imatinib and Sunitinib
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 199
- 主要终点
- Progression-free Survival
研究概览
简要总结
A randomized, double-blind, placebo-controlled phase III study of regorafenib plus best supportive care versus placebo plus best supportive care for subjects with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease has progressed despite prior treatment with at least imatinib and sunitinib.
The study is composed of 3 periods: A Screening Period, a Treatment Period, and a Survival Follow up Period.
Subjects randomized to be treated with regorafenib will receive 160 mg po od for 3 weeks of every 4 week (28 day) cycle (ie, 3 weeks on/1 week off). In addition subjects will receive best supportive care which excludes any disease specific anti cancer therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgery.
Tumor assessment will be every 4 weeks for the first 3 months, every 6 weeks for the next 3 months (through month 6), and every 8 weeks until the end of treatment, or more frequently if clinically indicated. Tumor assessments include CT or MRI and will be performed until tumor progression is seen in a central radiology review.
Subjects receiving placebo who experience disease progression may be offered active treatment.
Subjects who experience progression during regorafenib treatment may continue open label treatment.
All subjects will enter the Survival Follow-up Period upon discontinuation of randomized study treatment.
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
- •Male or female subjects 18 years of age.
- •Subjects with histologically confirmed metastatic and/or unresectable GIST.
- •At least imatinib and sunitinib as prior treatment regimens, with objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib therapy. Additionally, disease progression or intolerance to other systemic therapies, as well as investigational new agents, is allowed, except prior treatment with any other vascular endothelial growth factor receptor (VEGFR) inhibitor.
- •Subjects must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.
- •A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate bone marrow, liver, and renal function as assessed by laboratory parameters.
- •Recovery to NCI-CTCAE v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure-related toxicity (except alopecia and anemia).
排除标准
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
- •Congestive heart failure New York Heart Association (NYHA) class
- •Unstable angina (angina symptoms at rest, new-onset angina, ie, within the last 3 months) or myocardial infarction (MI) within the past 6 months before start of study medication.
- •Uncontrolled hypertension (systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management).
- •Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before start of study drug or venous thrombotic events such as deep vein thrombosis within the 3 months before start of study drug.
- •Ongoing infection grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.
- •Symptomatic metastatic brain or meningeal tumors.
- •Subjects with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event NCI-CTCAE version 4.0 grade 3 or higher within 4 weeks prior to the start of study drug.
- •Non-healing wound, ulcer, or bone fracture.
- •Persistent proteinuria of NCI-CTCAE version 4.0 grade 3 or higher (3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample).
研究组 & 干预措施
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
干预措施: Regorafenib (Stivarga, BAY73-4506) (Drug)
Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
干预措施: Best supportive care (Drug)
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
干预措施: Placebo (Drug)
Placebo
Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks
干预措施: Best supportive care (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year)
Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
次要结局
- Overall Survival(From randomization of the first subject until date of database cutoff (08 Jun 2015))
- Objective Response Rate(From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year.)
- Disease Control Rate (DCR)(From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year)
- Tumor Response(From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year)
- Time to Progression (TTP)(From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year)
- Duration of Response (DOR)(From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year)