An Open-label, Phase II Study of Vemurafenib in Patients With BRAF V600 Mutation-positive Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 34
- 主要终点
- Confirmed Best Overall Response Rate (BORR)
研究概览
简要总结
This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Must have recovered from all side effects of their most recent systemic or local treatment
- •Adequate hematological, renal and liver function
- •For solid tumors only:
- •Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
- •Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
- •For multiple myeloma only:
- •Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
- •Must have received at least one prior systemic therapy for the treatment of multiple myeloma
- •Treated with local radiotherapy
- •Must have relapsed and/or refractory multiple myeloma with measurable disease
排除标准
- •Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
- •Uncontrolled concurrent malignancy
- •Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
- •Active or untreated central nervous system (CNS) metastases
- •History of or known carcinomatous meningitis
- •Concurrent administration of any anti-cancer therapies other than those administered in this study
- •Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study
研究组 & 干预措施
Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib
Participants with NSCLC will be treated with vemurafenib monotherapy.
干预措施: vemurafenib (Drug)
Cohort 2: Ovarian Cancer - vemurafenib
Participants with ovarian cancer will be treated with vemurafenib monotherapy.
干预措施: vemurafenib (Drug)
Cohort 3a: Colorectal Cancer - vemurafenib
Participants with colorectal cancer will be treated with vemurafenib monotherapy.
干预措施: vemurafenib (Drug)
Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab
Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy.
干预措施: cetuximab (Drug)
Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab
Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy.
干预措施: vemurafenib (Drug)
Cohort 4: Cholangiocarcinoma - vemurafenib
Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy.
干预措施: vemurafenib (Drug)
Cohort 6: Multiple Myeloma - vemurafenib
Participants with multiple myeloma will be treated with vemurafenib monotherapy.
干预措施: vemurafenib (Drug)
Cohort 7: Other Solid Tumors - vemurafenib
Participants with Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), anaplastic thyroid cancer, advanced stage astrocytoma, early stage astrocytoma and other BRAF V600-positive tumors will be treated with vemurafenib monotherapy. Subcohorts will be analyzed separately if 7 or more participants are enrolled for each indication.
干预措施: vemurafenib (Drug)
结局指标
主要结局
Confirmed Best Overall Response Rate (BORR)
时间窗: Up to approximately 3 years
Confirmed BORR: percentage of participants with an objective response (OR) (complete response \[CR\], partial response \[PR\], stringent CR \[sCR\] or very good PR \[VGPR\]) on 2 occasions \>/= 4 weeks apart as assessed by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or International Myeloma Working Group (IMWG) criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: \>/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \</= 5% plasma cells in bone marrow; PR: \>/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>/= 90% or to \<200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hour; sCR: CR plus normal free light chain (FLC) ratio and no clonal cells in bone marrow.
次要结局
- Percentage of Participants With Confirmed Clinical Benefit(Up to approximately 3 years)
- Overall Response Rate (ORR)(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)
- Time to Response(Up to approximately 3 years)
- Time to Tumor Progression (TTP)(Up to approximately 3 years)
- Progression Free Survival (PFS)(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 3 years)
- Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab(Up to approximately 3 years)
- Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab(Up to 28 days)
- Safety: Percentage of Participants With Adverse Event(Up to approximately 3 years)