An Open Label, Multicenter, Phase I/IIB Study of Dacomitinib Plus Anlotinib for Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) 21-L858R Mutations.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Overall safety profile
研究概览
简要总结
This is a multicenter, open label, Phase I/IIB study investigating the efficacy and safety of treatment with dacomitinib plus anlotinib as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) 21-L858R mutations. This study comprises two parts: 1. A dose escalation Phase I study to determine the recommended phase II dose. 2. a multi-center, open label, randomized controlled, Phase IIB study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age and ≤75 years;
- •Provision of a voluntarily given, personally signed and dated, written informed consent document;
- •Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
- •It is acceptable for subjects with the presence of EGFR activating mutation (exon 19 deletion and the L858R mutation in exon 21) to be included in this Phase I study; Only subjects with the L858R mutation in exon 21 to be included in this Phase IIb;
- •At least one measurable disease by RECIST criteria version 1.1;
- •Patients with controlled or stable brain metastases;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
- •No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
- •Able to comply with required protocol procedures and able to receive oral medications;
- •Adequate organ function, including:
- •(1) Adequate bone marrow function Hemoglobin≥90g/L, absolute neutrophil count (ANC) should be ≥ 1.5x109/L, platelets should be ≥ 80x109/L; (2) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN), Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Creatinine≤ 1.5 x upper normal limit (ULN), or ≥ 60 mL/min; (3) Cardiac function: LVEF≥50% assessed by Doppler ultrasound；
排除标准
- •Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
- •Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
- •Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
- •Patients with pre-existing meningeal metastases;
- •Patients who have concurrent other malignant tumors;
- •Any history of hemoptysis, hematochezia, bloody sputum;
- •Tumor invasion or adjacent major vessels;
- •Patients with uncontrolled or significant systematic disease, including: active infection, thyroid dysfunction, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, or myocardial infarction within 6 months, or severe arrhythmia requiring medication;
- •A history of other diseases, or metabolic dysfunction, or physical examination or laboratory results suggestive of a disease or condition that precludes the use of an investigational drug, or may affect the interpretation of the study results, or expose the patient to a high risk of treatment complications;
- •Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;
- •Pregnant or lactating females;
- •Patients allergic to any pharmaceutical ingredient.
研究组 & 干预措施
Combined treatment group
Dacomitinib+Anlotinib: Patients will be treated with combined Dacomitinib and Anlotinib.
干预措施: Dacomitinib+Anlotinib (Drug)
Dacomitinib monotherapy group
Dacomitinib: Patients will be treated with Dacomitinib.
干预措施: Dacomitinib (Drug)
结局指标
主要结局
Overall safety profile
时间窗: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)
Overall safety profile of combined Dacomitinib plus Anlotinib in Escalation Phase, including adverse events (AE), as defined and graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE 4.03\], and first cycle Dose Limiting Toxicities (DLTs).
Progression Free Survival (PFS)
时间窗: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)
Progression Free Survival (PFS) is defined as the time from start of treatment to the date of disease progression as defined by RECIST v1.1 per investigator review or death due to any cause, whichever occurred first.
次要结局
- Best Overall Response (BOR)(From baseline until disease progression, up to 48 months)
- Overall Survival (OS)(48 months)
研究者
Baohui Han
Director of Respiratory Department
Shanghai Chest Hospital