An Open-label, Multicenter, Single-arm, Phase I Dose-escalation With Efficacy Tail Extension Study of Vemurafenib (RO5185426) in Pediatric Patients With Surgically Incurable and Unresectable Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 主要终点
- Maximum Tolerated Dose (MTD)/Recommended Dose
研究概览
简要总结
This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until disease progression or unacceptable toxicity occurs.
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
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric participants, 12 to 17 years of age inclusive
- •Histologically confirmed surgically incurable and unresectable Stage IIIC or Stage IV (AJCC) melanoma
- •Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation Test)
- •Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- •Performance status: Karnofsky (for participants >/= 16 years of age) or Lansky (for participants < 16 years of age) score of >/= 60
- •Adequate bone marrow, liver and renal function
- •Participants must have fully recovered from the acute toxic effects of all prior therapy prior to first administration of study drug
排除标准
- •Active or untreated central nervous system (CNS) lesions
- •History of or known spinal cord compression or carcinomatous meningitis
- •Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
- •Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ, and carcinoma in-situ of the cervix
- •Previous treatment with selective/specific BRAF or Methyl Ethyl Ketone (MEK) inhibitor (previous treatment with sorafenib is allowed)
- •Any previous treatment with study drug (RO5185426) or participation in a clinical trial that includes RO5185426
- •Pregnant or lactating females
- •Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS)-related illness, active hepatitis B virus, or active hepatitis C virus
研究组 & 干预措施
Vemurafenib
Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (>=)45 kilogram (kg) and other weighing less than (<)45 kg. The starting dose for participants (>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing <45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
干预措施: vemurafenib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)/Recommended Dose
时间窗: Up to 28 days of treatment
The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
次要结局
- Area Under the Concentration-Time Curve for Vemurafenib(Pre-dose, 2, 4, 8, 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days))
- Best Overall Response Rate (BORR)(Up to 2 years)
- Progression-free Survival (PFS)(Randomization date of first subject until disease progression or death or which ever occur first (2 years))
- Number of Participants With an Adverse Event (AE)(Up to approximately 2 years 11 months)
- Clinical Benefit Rate (CBR)(Up to 2 years)
- Overall Survival (OS)(Randomization date of first subject until death (2 years))