Multicenter 3-arm Trial to Evaluate the Efficacy and Safety of Pasireotide LAR or Everolimus Alone or in Combination in Patients With Well Differentiated Neuroendocrine Carcinoma of the Lung and Thymus - LUNA Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Percentage of Participants Progression-free at 9 Months Based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
研究概览
简要总结
This was a multicenter, randomized, phase II study evaluating Everolimus or Pasireotide LAR alone or in combination in adult patients with advanced (unresectable or metastatic) neuroendocrine carcinoma of the lung and thymus
详细描述
This was a prospective, multicenter, randomized, open-label, 3-arm, phase II study with a single-stage design in each arm. The purpose of this study was to test the effectiveness and safety of Everolimus or Pasireotide LAR alone or in combination in adult patients with advanced (unresectable or metastatic) neuroendocrine carcinoma (typical and atypical) of the lung and thymus. It was expected that a total of 120 patients with 40 patients in each arm were to be enrolled into this study. Patients were seen weekly for one month and monthly thereafter. Radiological and biochemical response assessments were performed every 3 months.
Patients with disease control (stable disease or better) in the combination arm or monotherapy with pasireotide LAR and everolimus who had not experienced unacceptable toxicity were permitted to continue treatment in the extension phase of the study and were seen every 3 months. Patients could remain in the extension phase as long as they continued to have clinical benefit and had not fulfilled any of the study discontinuation criteria. All patients had a safety follow-up visit 56 days after last treatment dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 confirmed advanced well differentiated typical and atypical carcinoid tumors of the lung or thymus
- •Patients of all treatment lines including naive patients could have been enrolled
- •At least one measurable lesion of disease on CT scan or MRI
- •Radiological documentation of disease progression within 12 months prior to randomization
- •Adequate liver, renal and bone marrow function
- •WHO Performance Status 0-2
排除标准
- •Poorly differentiated neuroendocrine carcinoma
- •Non-neuroendocrine thymoma
- •Patients with severe functional disease who required symptomatic treatment with somatostatin analogs
- •Prior therapy with mTOR inhibitors
- •History of liver disease
- •Baseline QTcF> 470 msec
- •Uncontrolled diabetes mellitus despite adequate therapy
研究组 & 干预措施
Pasireotide LAR
Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1
干预措施: Pasireotide LAR (Drug)
Everolimus
Everolimus 10 mg taken orally (p.o) once daily starting on Day 1
干预措施: Everolimus (Drug)
Pasireotide LAR and Everolimus Combination
Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
干预措施: Pasireotide LAR and Everolimus Combination (Drug)
结局指标
主要结局
Percentage of Participants Progression-free at 9 Months Based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
时间窗: Baseline up to 9 months
Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at Month 9 were to be considered as "progression-free" based on RECIST v1.1. Patients with missing tumor assessment, or with overall lesion response "unknown" at Month 9 were considered as "non progression-free", unless any of the following assessments at Week 48 or Week 52 indicate CR, PR, or SD, in which case the patient was to be considered as progression-free at Month 9. Patients discontinuing the study for any reason prior to the 9 month assessment were to be considered as "non progression-free".
次要结局
- Summary of Progression-free Survival (PFS) Based on RECIST v1.1(Baseline, every 3 months up to 69 months)
- Summary of Time to Response (Months)(Every 3 months up to Year 1)
- Kaplan-Meier Estimates of Progression-free Survival (PFS)(Baseline, every 3 months up to 69 months)
- 12-month Disease Control Rate (DCR) and Objective Response Rate (ORR)(Baseline up to Month 12)
- Kaplan-Meier Event-free Probability Estimate Based on CgA Levels(Baseline, every 3 months up to Month 18)
- Summary of Biochemical Progression-free Survival Based on CgA Levels by Treatment(Baseline up Month 24)
- Biochemical Response Rate (BRR) for Chromogranin A (CgA) Levels(Baseline up to Week 52)
- Biochemical Response Rate (BRR) for 5HIAA Levels(Baseline up Week 52)
- Summary of Duration of Response (Months)(Every 3 months up to Year 1)
- Duration of Biochemical Response (DBR), by Treatment (Full Analysis Set)(Baseline up to Month 18)
- Kaplan-Meier Event-free Probability Estimate for Biochemical Progression-free Survival Based on CgA Levels(Baseline, every 3 months up to Month 24)