An Open-label, Single-arm, Phase II, Multicenter Study, to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients With Brain Metastases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 146
- 主要终点
- Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])
研究概览
简要总结
This open-label, single-arm, multicenter study will evaluate the efficacy and safety in participants with metastatic melanoma who developed brain metastases. Participants may or may not have received prior systemic treatment for metastatic melanoma [except treatment with v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase (MEK) inhibitors]. Participants will receive oral doses of 960 mg vemurafenib twice daily until disease progression, unacceptable toxicity or consent withdrawal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adult participants, >/= 18 years of age
- •Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
- •Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
- •Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
- •Participants may or may not have symptoms related to their brain metastases
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
排除标准
- •Increasing corticosteroid dose during the 7 days prior to first dose of study drug
- •Leptomeningeal involvement in participants with no prior treatment for brain metastases
- •Previous malignancy requiring active treatment 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 anticancer therapies other than those administered in the study
- •Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
- •Prior treatment with BRAF or MEK inhibitors
- •Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug
研究组 & 干预措施
Cohort 1: Previously Untreated Participants
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
干预措施: Vemurafenib (Drug)
Cohort 2: Previously treated Participants
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])
时间窗: Baseline up to the disease progression or death from any cause (approximately 4 years)
BORR assessed by IRC is defined as percentage of participants who were responders \[with best overall response (BOR) documented as confirmed complete response (CR) or partial response (PR)\]. The RECIST v1.1 criteria modified for independent review of body and brain lesions was based on current radiology practices. The modifications to RECIST v1.1 included allowing target lesions in the brain to be \>=5 mm by contrast-enhanced magnetic resonance imaging scan (in traditional RECIST v1.1 this is \>=10 mm), allowing up to 5 target lesions in the brain (in traditional RECIST v1.1 only 2 target lesions), and examining the lesions within the brain and outside the brain separately for analytical purposes. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm), PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Duration of Response (DOR) (Assessed by Investigator and IRC)(Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years))
- Overall Survival(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator)(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1(Baseline up to the disease progression or death from any cause (approximately 4 years))
- Time to Development of New Brain Metastases in Responders(Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years))
- Percentage of Participants With Adverse Events (AE)(From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years))
- Best Overall Response Rate Outside the Brain (Assessed by IRC)(Baseline up to the disease progression or death from any cause (approximately 4 years))