An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 15
- 主要终点
- Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
研究概览
简要总结
This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma. Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d. continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability. Target sample size is <100 patients.
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
- •adult patients >/=18 years of age
- •histologically confirmed metastatic melanoma (Stage IV, AJCC)
- •patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
- •BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
- •measurable disease by RECIST criteria
- •negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
排除标准
- •active CNS metastases on CT/MRI within 28 days prior to enrollment
- •history of or known carcinomatous meningitis
- •previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
- •cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
- •uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
- •infectious disease including HIV, HBV and HCV
研究组 & 干预措施
Single arm
干预措施: vemurafenib (Drug)
结局指标
主要结局
Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
时间窗: From first treatment through September 27, 2010
BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
次要结局
- Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1(Pre-dose to 8 hours post-dose on Day 15 of Cycle 1)
- Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1(Pre-dose to 8 hours post-dose on Day 15 of Cycle 1)
- Vemurafenib Plasma Levels at Various Treatment Cycles(Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1)
- Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)(From first treatment through September 27, 2010)
- Overall Survival(From first treatment through September 27, 2010)
- Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline(From first treatment through September 27, 2010)
- Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)(From first treatment through September 27, 2010)
- Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)(From first treatment through September 27, 2010)
- Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)(From first treatment through September 27, 2010)
- Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)(Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1)
- Percentage of Patients With Adverse Event(From first treatment through September 27, 2010)