A Phase Ib/II Study of Docetaxel With or Without Buparlisib as Second Line Therapy for Patients With Advanced or Metastatic Squamous Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
研究概览
简要总结
This is a multi-center, open-label Phase Ib dose escalation part followed by a randomized double-blinded placebo controlled Phase II part.
The Phase Ib part will determine the Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of buparlisib in combination with docetaxel. Subsequently the MTD/RP2D will be investigated in a Phase II randomized trial in patients with advanced or metastatic squamous NSCLC.
详细描述
Based on an overall review of safety and preliminary efficacy data done on 01-Dec-2014 showing marginal anti-tumor activity and newly emerged treatment options, a decision was taken to stop further development of this combination in patients with advanced or metastatic squamous NSCLC and Phase II of the study was not conducted.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 is an adult ≥ 18 years old at the time of informed consent
- •Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous and non-squamous or adenosquamous NSCLC will be acceptable for enrollment.
- •Patient has received one prior approved regimen of platinum-based chemotherapy (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) squamous NSCLC, followed by disease progression. A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.
- •Note: Patients who received paclitaxel therapy are eligible for this trial. •Patient has adequate tumor tissue (either archival or new tumor biopsy) for the analysis of PI3K-related biomarkers.
- •Enrollment in the Phase II part of the study is contingent on the central laboratory confirming receipt of an adequate amount of tissue including sufficient DNA for analysis.
- •Patient has measurable or non-measurable disease according to RECIST version 1.1 criteria.
- •Phase II only: Patient must have at least one measurable lesion as per RECIST criteria.
- •Patient has an ECOG performance status ≤ 1
- •Patient has adequate bone marrow and organ function
排除标准
- •Patient has received previous treatment with a PI3K or AKT inhibitor
- •Patient has symptomatic Central Nervous System (CNS) metastases Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed prior local treatment, if any, for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery, or ≥ 14 days for stereotactic radiosurgery).
- •Patient has a score ≥ 12 on the PHQ-9 questionnaire.
- •Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9).
- •Patient has a GAD-7 mood scale score ≥
- •Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation or patients with active severe personality disorders.
- •Patient has ≥ CTCAE grade 3 anxiety
研究组 & 干预措施
Phase Ib: Buparlisib + docetaxel
Buparlisib (BKM120) oral once daily: 80 mg and 100 mg dose levels to be tested in the dose escalation part of the trial in combination with docetaxel every three week intravenous (i.v.) infusion: 75 mg/m2 as per label.
干预措施: Buparlisib (Drug)
Phase Ib: Buparlisib + docetaxel
Buparlisib (BKM120) oral once daily: 80 mg and 100 mg dose levels to be tested in the dose escalation part of the trial in combination with docetaxel every three week intravenous (i.v.) infusion: 75 mg/m2 as per label.
干预措施: Docetaxel (Drug)
Phase II: Buparlisib + docetaxel
Buparlisib oral once daily: MTD/RP2D mg to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.
干预措施: Buparlisib (Drug)
Phase II: Buparlisib + docetaxel
Buparlisib oral once daily: MTD/RP2D mg to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.
干预措施: Docetaxel (Drug)
Phase II: Placebo + docetaxel
Buparlisib matching placebo oral once daily to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.
干预措施: Buparlisib matching placebo (Drug)
Phase II: Placebo + docetaxel
Buparlisib matching placebo oral once daily to be tested in combination with docetaxel every three week i.v. infusion: 75 mg/m2 as per label.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
时间窗: Day 21
To determine the maximum tolerated dose/recommended phase ll dose (MTD/RP2D) of buparlisib in combination with docetaxel by assessing the incidence of DLTs in Cycle 1; Cycle 1 = 21 days
Phase II: Progression Free Survival (PFS)
时间窗: After 70 PFS events have been observed at 9 months after patient enrollment
PFS as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. To estimate the treatment effect of docetaxel and buparlisib or placebo on PFS in patients with advanced or metastatic squamous NSCLC.
次要结局
- Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30(Baseline, Every 6 weeks until disease progression for up to 3 years)
- Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30(Baseline, Every 6 weeks until disease progression for up to 3 years)
- Time to response (ToR)(Every 6 weeks from randomization until first documented progression for up to 3 years)
- Number of patients with at least one adverse event.(Up to 30 days after the last dose)
- Overall Survival (OS)(Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years)
- Overall response rate (ORR)(Every 6 weeks from randomization until first documented progression for up to 3 years)
- Number of patients with laboratory abnormalities.(Up to 30 days after the last dose)
- Changes in vital signs(Up to 30 days after the last dose)
- Docetaxel and buparlisib plasma concentrations(Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1)
- PFS Phase Ib(at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years)
- Duration of response (DR)(Every 6 weeks from randomization until first documented progression for up to 3 years)
- Change in electrocardiogram (ECG) and cardiac imaging(Up to 30 days after the last dose)
- Shift in ECOG performance status(Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years))
- Change in Mood scales(Up to 30 days after the last dose)