An Exploratory Study of the Immunological Effects of Vemurafenib and Cobimetinib, Administered Alone and in Combination, in Subjects With Advanced BRAF V600E/K Mutant Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
研究概览
简要总结
This trial explores the immunologic effects of vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor), administered alone and in combination, to patients with advanced BRAF V600E/K mutant melanoma.
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
- 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
- •Signed informed consent
- •Signed HIV testing consent
- •Life expectancy ≥ 12 weeks
- •Able to swallow pills
- •ECOG performance status 2 or less
- •Adequate bone marrow function
- •Adequate renal function
- •Adequate liver function
- •Negative urine pregnancy test within 7 days prior to commencement of dosing in premenopausal women
- •Histological diagnosis of unresectable AJCC stage III or stage IV, BRAFV600E/K mutant melanoma
- •Measurable disease
- •Accessible tumor that can be biopsied
- •Naive to targeted therapy (Prior immune-based therapy in the adjuvant setting or for advanced disease will be allowed if >2 weeks from study entry)
排除标准
- •Active systemic infection
- •Active autoimmune disease or history of known or suspected autoimmune disease
- •Active brain metastases or leptomeningeal metastases
- •Treatment with any immunomodulatory medication within 4 weeks of initiation of study therapy.
- •Positive test for hepatitis B virus
- •Positive test for hepatitis C virus
- •Positive test for human immunodeficiency virus (HIV)
- •Pregnant, lactating or breast feeding women
- •Localized radiation therapy within the last 14 days
- •History of malabsorption
- •No consumption of the following within 7 days prior to start of treatment:
- •St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
- •Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor
- •History or evidence of cardiovascular risk
- •History or evidence of retinal pathology
研究组 & 干预措施
Cohort 1
Ten patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.
干预措施: Cobimetinib (Drug)
Cohort 1
Ten patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.
干预措施: Vemurafenib (Drug)
Cohort 2
Ten patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.
干预措施: Cobimetinib (Drug)
Cohort 2
Ten patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
时间窗: 2 years
compare immunologic changes described above with the development of study treatment-related adverse events. For example, severity or extent of rash from cobimetinib (a well-described dermatologic toxicity of MEK inhibitors) may be compared to levels of intratumoral immune activation assessed by one or more of the parameters.
次要结局
- Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.(2 years)