A Phase I-II Evaluation of the Safety and Efficacy of the Oral HSP90 Inhibitor Debio 0932 in Combination With Standard of Care in first-and Second-line Therapy of Patients With Stage IIIb or IV Non-small Cell Lung Cancer-the HALO Study (HSP90 Inhibition And Lung Cancer Outcomes)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 82
- 试验地点
- 8
- 主要终点
- Occurrence of Dose Limiting Toxicities
研究概览
简要总结
Part A of this study will investigate the Maximum Tolerated Dose of Debio 0932 in combination with standard of care chemotherapy for the first- and second-line treatment of advanced NSCLC.
详细描述
Part A of this study will determine the Maximum Tolerated Dose of Debio 0932 in combination with cisplatin/pemetrexed and cisplatin/gemcitabine in treatment-naïve patients with Stage IIIb or IV NSCLC, and with docetaxel in previously treated patients with Stage IIIb or IV NSCLC.
Escalating doses of Debio 0932 will be given to subsequent patients in combination with standard doses of these 3 background chemotherapies.
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
- •Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known epidermal growth factor receptor (EGFR) mutation
- •Advanced or metastatic disease (Stage IIIb or IV)
- •Patients to be treated with cisplatin/gemcitabine or cisplatin/pemetrexed: No previous systemic treatment with chemotherapy, targeted therapy or investigational agents (except adjuvant therapy if > 6 months ago); Patients to be treated with docetaxel: ≥ 1 previous treatment with chemotherapy
- •Measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •ECOG performance score 0-1
- •Life expectancy ≥ 3 months
- •Adequate bone marrow-, renal- and hepatic function
- •LVEF ≥ 55% on cardiac ultrasound
排除标准
- •Symptomatic brain metastases
- •Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn's disease)
- •Concurrent treatment with any other systemic anti-cancer therapy
- •Serious concomitant uncontrolled medical conditions
研究组 & 干预措施
Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Pemetrexed, Debio 0932
干预措施: Pemetrexed (Drug)
Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Pemetrexed, Debio 0932
干预措施: Debio 0932 (Drug)
Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Pemetrexed, Debio 0932
干预措施: Cisplatin (Drug)
Cisplatin, Gemcitabine, Debio 0932
Cisplatin, Gemcitabine, Debio 0932
干预措施: Debio 0932 (Drug)
Cisplatin, Gemcitabine, Debio 0932
Cisplatin, Gemcitabine, Debio 0932
干预措施: Cisplatin (Drug)
Cisplatin, Gemcitabine, Debio 0932
Cisplatin, Gemcitabine, Debio 0932
干预措施: Gemcitabine (Drug)
Docetaxel, Debio 0932
Docetaxel, Debio 0932
干预措施: Debio 0932 (Drug)
Docetaxel, Debio 0932
Docetaxel, Debio 0932
干预措施: Docetaxel (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicities
时间窗: 6 weeks
次要结局
- Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1(22 days)
- Pharmacodynamic biomarkers(22 days)
- Change in left ventricular ejection fraction (LVEF)(Baseline and after 4 weeks of treatment)
- Best overall tumor response(22 days)
- Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932(7 days)
- Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS)(Day 1 of each treatment cycle until disease progression or study drug toxicity)
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Every treatment cycle until disease progression or study drug toxicity)
- Incidence of laboratory abnormalities(2 to 4 times every treatment cycle until disease progression or study drug toxicity)
- Incidence of treatment discontinuations due to AEs and SAEs(Every treatment cycle until diseases progression or study drug toxicity)
- Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel(22 days)