A Phase III, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib Plus GDC-0973 in Previously Untreated BRAF^600-Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 495
- 试验地点
- 156
- 主要终点
- Progression-free Survival
研究概览
简要总结
To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by progression-free survival (PFS), assessed by the study site investigator.
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
- Triple (Participant, 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
- •Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
- •Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
- •Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
- •Measurable disease per RECIST v1.1
- •Eastern Clinical Oncology Group performance status of 0 or 1
- •Consent to provide archival for biomarker analyses
- •Consent to undergo tumor biopsies for biomarker analyses
- •Life expectancy greater than or equal to (≥) 12 weeks
- •Adequate hematologic and end organ function
排除标准
- •History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
- •Palliative radiotherapy within 14 days prior to the first dose of study treatment
- •Major surgery or traumatic injury within 14 days prior to first dose of study treatment
- •Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
- •History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
- •Uncontrolled glaucoma with intraocular pressure
- •Serum cholesterol ≥ Grade 2
- •Hypertriglyceridemia ≥ Grade 2
- •Hyperglycemia (fasting) ≥ Grade 2
- •History of clinically significant cardiac dysfunction
- •Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:
- •All known CNS lesions have been treated with stereotactic therapy or surgery, AND
- •There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
- •Current severe, uncontrolled systemic disease
- •History of malabsorption or other condition that would interfere with absorption of study drugs
- •Pregnant, lactating, or breast feeding women
研究组 & 干预措施
Placebo + Vemurafenib
Participants will receive placebo orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 milligrams (mg) orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
干预措施: Placebo (Drug)
Placebo + Vemurafenib
Participants will receive placebo orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 milligrams (mg) orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
干预措施: Vemurafenib (Drug)
Cobimetinib + Vemurafenib
Participants will receive cobimetinib 60 mg orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
干预措施: Vemurafenib (Drug)
Cobimetinib + Vemurafenib
Participants will receive cobimetinib 60 mg orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
干预措施: Cobimetinib (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
次要结局
- Overall Survival(Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months))
- Percentage of Participants With an Objective Response(Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months))
- Duration of Response(Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months))