Efficacy and Safety of Lanreotide ATG 120 mg in Combination With Temozolomide in Subjects With Progressive Well Differentiated Thoracic Neuroendocrine Tumors. A Phase II, Multicentre, Single Arm, Open-label Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 40
- 试验地点
- 10
- 主要终点
- Disease Control Rate (DCR) Assessed Locally at Month 9
研究概览
简要总结
The purpose of the protocol is to evaluate the efficacy and safety of Lanreotide ATG 120 mg in combination with Temozolomide in subjects with unresectable advanced neuroendocrine tumours of the lung or thymus as Disease Control Rate at 9 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histological documented unresectable advanced (locally or metastatic) well or moderately differentiated neuroendocrine tumors of the lung or thymus (typical and atypical carcinoids according to the World Health Organisation (WHO) 2004 criteria);
- •Imaging documented progression within 12 months before screening visit (V1), according to RECIST criteria v 1.1;
- •Measurable disease, as defined by RECIST criteria v 1.1, on a CT scan performed at screening visit (V1);
- •Octreoscan or Ga68-DOTA-TATE/TOC/NOC-PET-TC within 12 months before screening visit (V1);
- •Adequate liver, renal and bone marrow function.
排除标准
- •Poorly differentiated neuroendocrine carcinoma and mixed Neuroendocrine tumours (NET), according to WHO 2004 criteria
- •Neuroendocrine tumours other than lung or thymus
- •Non-neuroendocrine thymic neoplasm
- •Received a prior therapy with Peptide Receptor Radionuclide Therapy (PRRT) within 6 months prior to screening visit (V1)
- •Treated with systemic therapies (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies) within 1 month prior to screening visit (V1)
- •Treated with a number of systemic therapy lines > 3 prior to screening visit (V1), and any of the following:
- •for chemotherapy no more than 1 line prior to V1
- •for somatostatin analogue no more than 1 line therapy, considered as treatment lasting more than 6 months, prior to V1 no therapy with Temozolomide (TMZ) prior to V1
- •Received a prior therapy with Peptide Receptor Radionuclide Therapy (PRRT) within 6 months prior to screening visit (V1)
- •Received external palliative radiotherapy within the last 28 days prior to screening visit (V1)
- •Received locoregional therapies (Transarterial embolization, Transcatheter arterial chemoembolization, thermo-ablation with radio-frequency) and Selective internal radiotherapy within 3 months prior to screening visit (V1)
- •Presence of symptomatic brain metastasis
- •Subjects with symptomatic cholelithiasis at screening visit (V1)
研究组 & 干预措施
Lanreotide (Autogel formulation) and Temozolomide
Lanreotide ATG 120 mg every 28 days, deep subcutaneous injection for a maximum of 48 weeks, for a total number of 12 injections.
Temozolomide 250 mg hard capsules, for 5 consecutive days every 28 days, oral route, for a maximum of 48 weeks.
干预措施: Lanreotide (Autogel formulation) and Temozolomide (Drug)
结局指标
主要结局
Disease Control Rate (DCR) Assessed Locally at Month 9
时间窗: Up to Month 9; for sensitivity analysis-2, up to 10.5 months
Responders were participants who showed disease control according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v 1.1 assessed locally by the investigator. The DCR was defined as complete response (CR), partial response (PR) or stable disease (SD) according to RECIST criteria v1.1. A sensitivity analysis-1 of local DCR was performed excluding participants withdrawn before 9 months with reason other than progressive disease (PD) or missing assessment and considering participants with PD prior or at 9 months as failures. In addition, a sensitivity analysis-2 was performed in order to consider assessments done between 7.5 and 10.5 months as 9 months assessments when 9-month assessment was missing using same methodology, i.e. considering PD prior or at 9 months and participants withdrawn with other or missing reasons as failures.
次要结局
- DCR Assessed Centrally at Month 9(Up to Month 9)
- Median Time to Progression (TTP) Assessed Locally and Centrally(From Day 1 up to end of study, 52 weeks)
- Best Overall Response (BOR) Assessed Locally and Centrally(From Day 1 up to end of study, 52 weeks)
- Objective Response Rate (ORR) Assessed Locally and Centrally at Months 9 and 12(Months 9 and 12)
- DCR Assessed Locally and Centrally at Month 12(Month 12)
- DCR Assessed Locally and Centrally at Month 9 by Carcinoid Type(Up to Month 9)
- Percentage of Biochemical Responders According to Chromogranin A (CgA) Plasma Levels(Baseline (Day 1) and Week 4, 12, 24, 36 and 52)
- Neuron-Specific Enolase (NSE) and CgA Biomarker Levels(Baseline and Weeks 4, 12, 24, 36 and 52)
- Influence of Biomarkers Expression on Locally and Centrally Assessed PFS(From Screening period (-4 weeks) up to Week 52)
- Influence of Biomarkers Expression on Locally and Centrally Assessed ORR at Months 9 and 12(Screening period, Months 9 and 12)
- Median Progression Free Survival (PFS) Assessed Locally and Centrally(From Day 1 up to end of study, 52 weeks)
- Median Time to Response (TTR) Assessed Locally and Centrally(From Day 1 up to end of study, 52 weeks)
- Median Duration of Response (DOR) Assessed Locally and Centrally(From Day 1 up to end of study, 52 weeks)
- Influence of Biomarkers Expression on Locally and Centrally Assessed DCR at Months 9 and 12(Screening period, Months 9 and 12)
- Coefficient of Agreement Between Central and Local Assessment of Tumor Radiological Response at Month 9(Month 9)