BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 675
- 主要终点
- Overall Survival
研究概览
简要总结
This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.
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
- •adults, >/=18 years of age
- •metastatic melanoma, stage IIIC or IV (AJCC)
- •treatment-naïve (no prior systemic anticancer therapy)
- •positive for BRAF V600E mutation
- •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 central nervous system metastases
- •history of carcinomatous meningitis
- •severe cardiovascular disease within 6 months prior to study drug administration
- •previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix
研究组 & 干预措施
Dacarbazine
干预措施: Dacarbazine (Drug)
Vemurafenib
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3).
An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
Progression-free Survival
时间窗: From randomization (initiated January 2010) to December 30 2010.
A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).
次要结局
- Duration of Response(From randomization (initiated in January 2010) until December 30, 2010.)
- Participants With a Best Overall Response (BOR) of Complete Response or Partial Response(From randomization (initiated January 2010) until December 30, 2010)
- Time to Confirmed Response(From randomization (initiated January 2010) until December 30, 2010.)
- Number of Participants With Adverse Events (AEs)(From randomization (initiated January 2010) until December 30, 2010.)
- Pre and Post-dose Plasma Vemurafenib Concentration by Study Day(Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190).)
- Time to Treatment Failure(approximately 3 years)