An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 主要终点
- Best Overall Response Rate in TKI-Naive Participants
研究概览
简要总结
This open-label, multi-center study will evaluate the safety and efficacy of Vemurafenib (RO5185426) in participants with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until progressive disease or unacceptable toxicity occurs.
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 or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective; participants whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary
- •Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test)
- •Radioactive Iodine resistant disease
- •Prior therapy excluding (Cohort 1, TKI Naive) or including (Cohort 2, TKI Experienced) TKI
- •Clinically relevant disease progression according to RECIST criteria within the prior 14 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate hematological, renal and liver function
排除标准
- •Histological diagnosis other than papillary PTC, including squamous cell variants of PTC or PTC with areas of squamous metaplasia
- •Active or untreated central nervous system metastases
- •History of or known carcinomatous meningitis
- •Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study
- •Active squamous cell skin cancer that has not been excised or adequately healed post excision
- •Previous treatment with any agent that specifically and selectively targets the MEK or BRAF pathway
- •Prior radiotherapy to the only measurable lesion
- •Clinically relevant cardio-vascular disease or event within the prior 6 months
研究组 & 干预措施
Tyrosine Kinase Inhibitor (TKI) Naive
Vemurafenib in participants naive to any prior systemic TKI therapy.
干预措施: Vemurafenib (Drug)
TKI Experienced
Vemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR).
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Best Overall Response Rate in TKI-Naive Participants
时间窗: Up to approximately 4 years
Best overall response rate was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Best overall response rate: the percentage of participants with best objective response of complete response (CR) or partial response (PR) (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \< 10 millimeters (mm). PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.
次要结局
- Percentage of Participants With Adverse Events(Baseline until 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 4 years))
- Best Overall Response Rate in TKI-Experienced Participants(Up to approximately 4 years)
- Duration of Response(From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years))
- Progression-Free Survival(From the day of first treatment until the first documented PD or death (up to approximately 4 years))
- Clinical Benefit Rate(Up to approximately 4 years)
- Overall Survival(From the date of first treatment to the date of death for any cause (up to approximately 4 years))
- Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)(Up to approximately 4 years)