An Open-Label Pilot Study to Evaluate the Efficacy and Safety of a Combination Treatment of Sonidegib (LDE225) and Buparlisib (BKM120) For the Treatment of Advanced Basal Cell Carcinomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This pilot trial studies how well sonidegib and buparlisib work in treating patients with basal cell carcinoma that has spread to other places in the body. Sonidegib and buparlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
Estimate the overall response rate (ORR) of sonidegib (erismodegib) in combination with buparlisib (hereby referred to as "LB therapy") for patients with locally advanced or metastatic basal cell carcinoma (BCC) in Smoothened inhibitor-naive patients (Cohort 1) and those whose disease is refractory or relapsed on Smoothened inhibitor monotherapy (Cohort 2).
NOTE: This study does not compare the treatment effect between these 2 dissimilar participant groups.
SECONDARY OBJECTIVES:
- Estimate the median duration of response, on or after LB therapy.
- Assess the safety and tolerability of LB therapy.
- Assess the histopathologic effect of LB therapy in tumor biopsies obtained at baseline and following 12 weeks of treatment.
- Assess the effect of LB therapy on gene expression including Hedgehog pathway and phosphatidylinositol 3-kinase (PI3K) pathways.
- Assess correlation between gene mutations in Smoothened, suppressor of fused homolog (Sufu), patched (PTCH), glioma-associated oncogene homolog (Gli)1, 2 and gene expression profiles and response to LB therapy.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BCC refractory or relapsed after Smoothened inhibitor
Participants with locally advanced or metastatic basal cell carcinoma (BCC) that is refractory or relapsed after treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Buparlisib (Drug)
BCC Smoothened inhibitor-naive
Participants with locally advanced or metastatic basal cell carcinoma (BCC) and naive to treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Buparlisib (Drug)
BCC Smoothened inhibitor-naive
Participants with locally advanced or metastatic basal cell carcinoma (BCC) and naive to treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Sonidegib (Drug)
BCC refractory or relapsed after Smoothened inhibitor
Participants with locally advanced or metastatic basal cell carcinoma (BCC) that is refractory or relapsed after treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Sonidegib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 2 years
Response was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, and reported as overall response rate (ORR), comprised of the sum of complete response (CR) rate and partial response (PR) rate. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR
次要结局
- Median Duration of Response(up to 12 weeks)
- Adverse Event Frequency(Up to 30 days post-treatment)
- Changes in Gene Expression Profiles of BCCs Including Hedgehog Pathway and PI3K Pathways(Baseline to 2 years)
- Gene Expression Profiles (Correlation of Particular Gene Expression Profiles and Response to LB Therapy Will be Assessed.)(up to 2 years post-treatment)
研究者
Anne Chang
Associate Professor of Dermatology
Stanford University