Double Blind, Placebo Controlled Study Assessing the Efficacy of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Patients With Platinum Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 157
- 试验地点
- 8
- 主要终点
- Progression Free Survival (PFS) Per Investigator Assessment
研究概览
简要总结
Phase II Study of efficacy and safety of buparlisib (BKM120) plus paclitaxel versus placebo plus paclitaxel in recurrent or metastatic Head and Neck cancer previously pre-treated with a platinum therapy.The primary endpoint was PFS and the key secondary endpoint was Overall Survival.
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
- Double (Participant, Investigator)
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
- •Patient has histologically/cytologically-confirmed HNSCC.
- •Patient has archival or fresh tumor tissue for the analysis of PI3K-related biomarkers. One tumor block (preferred) or a minimum of 12 unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue.
- •Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed
- •Measurable disease as determined by per RECIST criteria v1.
- •If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a 4 week period since radiotherapy completion is required
- •Adequate bone marrow function and organ function
- •ECOG Performance Status ≤ 1
排除标准
- •Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;
- •Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease
- •Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;
- •Patient has not recovered to ≤ grade 1 (except alopecia) from related side effects of any prior antineoplastic therapy
- •Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ≤ 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF > 480 msec on the screening ECG (using the QTcF formula);
研究组 & 干预措施
Buparlisib + weekly Paclitaxel
Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
干预措施: Buparlisib (Drug)
Buparlisib + weekly Paclitaxel
Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
干预措施: Paclitaxel (Drug)
Buparlisib matching placebo + Paclitaxel
Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
干预措施: Buparlisib matching Placebo (Drug)
Buparlisib matching placebo + Paclitaxel
Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Per Investigator Assessment
时间窗: 4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years
PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date.
次要结局
- Overall Response Rate (ORR) as Per Local Radiological Assessment(4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years)
- Overall Survival (OS)(4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years)
- Time to Response (TTR) as Per Local Radiological Assessment(4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years)
- Disease Control Rate (DCR) as Per Local Radiological Assessment(4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years)
- Duration of Response (DoR) as Per Local Investigator(4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years)
- Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30(Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years)
- Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35(Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years)
- Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax(Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15)
- Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast(Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15)
- Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax(Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15)
- Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F(Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15)