An Open-Label, Multicenter Study to Assess the Safety of RO5185426 (Vemurafenib) in Patients With Metastatic Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 3,219
- 试验地点
- 280
- 主要终点
- Percentage of Participants Experiencing Any Grade 3 or 4 Adverse Events (AEs) as Determined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.0
研究概览
简要总结
This multi-center study evaluates the safety and efficacy of vemurafenib in participants with BRAF V600 mutation-positive, surgically incurable, and unresectable Stage IIIC or IV (American Joint Committee on Cancer [AJCC]) metastatic melanoma.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with Histologically confirmed metastatic melanoma (surgically incurable and unresectable Stage IIIC or Stage IV; AJCC) with BRAF V 600 mutation determined by Cobas 4800 BRAF Mutation Test. Unresectable Stage IIIC disease must have had confirmation from a surgical oncologist
- •Participants with either measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
- •Participants may or may not have received prior systemic therapy for metastatic melanoma
- •Eastern Cooperative Oncology Group (ECOG) performance status between 0 to 2
- •Adequate hematologic, renal and liver function
排除标准
- •Evidence of symptomatic central nervous system (CNS) lesions, use of steroids or anti-seizure medications for treatment of brain metastases prior to the first administration of vemurafenib
- •Previous malignancy (other than melanoma) within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
- •Concurrent administration of any anti-cancer therapies other than those administered in the study
- •Clinically significant cardiovascular disease or event within the 6 months prior to first administration of study drug
- •Refractory nausea or vomiting, external biliary shunt, or significant bowel resection that would preclude adequate absorption
研究组 & 干预措施
Vemurafenib
Participants will receive vemurafenib at a dose of 960 milligrams (mg) twice daily (bid) until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death, or study termination by the Sponsor, whichever occurs first.
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Any Grade 3 or 4 Adverse Events (AEs) as Determined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.0
时间窗: Baseline up to 28 days post end of treatment (maximum up to 46 months)
The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the NCI-CTCAE version 4.0, where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: Grade 3 means "Severe"; Inability to work or perform normal daily activity; treatment or medical intervention is indicated in order to improve the overall well-being or symptoms; delaying the onset of treatment is not putting the survival of the participant at direct risk. Grade 4 means "Life-threatening, Disabling"; based on extreme limitation in activity; significant medical intervention/therapy required; and hospitalization probable.
Mean Cumulative Dose of Vemurafenib
时间窗: Baseline up to end of treatment or death (maximum up to 46 months)
Duration of Vemurafenib Treatment
时间窗: Baseline up to end of treatment or death (maximum upto 46 months)
Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation.
Percentage of Participants With AEs of Special Interest
时间窗: Baseline up to 28 days post end of treatment (maximum up to 46 months)
AEs of special interest included cutaneous squamous cell carcinoma (SCC), rash, photosensitivity, liver injury, arthralgia, fatigue, gastrointestinal (GI) polyps, pancreatitis, potentiation of radiation toxicity, prolongation of cardiac repolarization or arrhythmia, non-cutaneous SCC and other primary malignancies (other than cutaneous SCC or new primary melanoma).
Percentage of Participants With at Least 1 AE Leading to Study Drug Interruption or Drug Discontinuation
时间窗: Baseline up to 28 days post end of treatment (maximum up to 46 months)
An AE was considered as any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Pre existing conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Percentage of participants with dose interruption or discontinuation due to AE was presented.
Mean Total Vemurafenib Dose Per Day
时间窗: Baseline up to end of treatment or death (maximum up to 46 months)
Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation. Average total dose per day: total actual dose taken divided by total actual days on treatment.
Dose Intensity of Vemurafenib
时间窗: Baseline up to end of treatment or death (maximum upto 46 months)
Dose intensity was defined as (total actual doses taken/total planned doses) \*100, where total planned doses = prescribed doses \* planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose.
次要结局
- Percentage of Participants With Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR), as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(Baseline until first documentation of confirmed CR or PR (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months]))
- Percentage of Participants With Improvement in Eastern Cooperative Group (ECOG) Performance Status(Baseline, Day 1 of each 28 day cycle up to end of treatment (up to 46 months))
- Percentage of Participants Who Received Any Concomitant Medications(Baseline up to 46 months)
- Percentage of Participants With PD Assessed According to RECIST v1.1 or Death(Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months]))
- Duration of Response(From 1st documentation of confirmed CR or PR to PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until end of the study [up to 46 months]))
- Progression Free Survival (PFS)(Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months]))
- Time to Response(Baseline until first documentation of confirmed CR or PR, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months]))
- Percentage of Participants Who Died(Baseline until death (maximum up to 46 months))
- Overall Survival (OS)(Baseline until death (maximum up to 46 months))