A Phase II Study of Neoadjuvant Double-drug Chemotherapy With Platinum Plus Anlotinib Hydrochloride in Stage III(N2) Non-small-cell Lung Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Lymph node(N2)downstage rate
研究概览
简要总结
Stage III non-small-cell lung cancer (NSCLC) is seen in a relatively heterogeneous group of patients with ipsilateral mediastinal (N2) lymph node involvement. The relative roles of different treatment modalities are not clear. The purpose of this study is to evaluate the efficacy and safety of neoadjuvant double-drug chemotherapy containing platinum plus anlotinib hydrochloride in patients with stage III(N2) non-small-cell lung cancer.
详细描述
This is a prospective, open-label, multi-institutional, positive medicine control of equal rank comparative study of neoadjuvant double-drug chemotherapy with platinum plus anlotinib hydrochloride in stage III(N2) non-small-cell lung cancer.The main purpose of this study was to compare the difference in N2 downgrade rate of lymph node and resectability rate between the experimental and control groups, to evaluate the efficacy of anlotinib hydrochloride, and to observe and evaluate its objective response rate(ORR)，Disease-free Survival (DFS)and overall survival(OS).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age :18 Years to 75 Years (Adult, Older Adult)
- •Pathological diagnosis with Stage III-N2 NSCLC which is clinically resectable and the N2 is diagnosed by either mediastinoscopy,EBUS,PET/CT;
- •EGFR、ALK、ROS1 mutation-negative；Patients with squamous cell carcinoma may not have genetic testing;PD-L1<5%;
- •According to the RECIST 1.1 standard, there is at least one measurable target lesion;
- •ECOG physical score 0-1 points; expected survival time ≥ 3 months;
- •The main organ function meets the following criteria:1)blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L;2)Blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
- •Subjects voluntarily joined the study and signed informed consent, with good adherence and follow-up.
排除标准
- •Stage I, II , IV orNSCLC;
- •Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);central lung squamous carcinoma along with cavum;
- •Patients with contraindication of chemotherapy
- •Subjects who have previously used Anlotinib;
- •Systematic anti-tumor treatments have been performed for the past 2 weeks, including chemotherapy, radiotherapy (except for metastatic lesions other than thoracic radiation), targeted therapy, immunotherapy, and biotherapy;
- •Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor;
- •A history of active bleeding within the first 6 months of screening, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
- •A thrombotic event occurs within 6 months (including arteriovenous thrombosis, pulmonary embolism, cerebrovascular accident, including transient ischemic attack, etc.);
- •Cardiac diseases with obvious clinical symptoms, such as: congestive heart failure, coronary heart disease with obvious symptoms, arrhythmia with difficult drug control (including clinically significant QTc interval prolongation history, or screening period QTc interval women >470ms, Male > 450ms), had myocardial infarction within 6 months, or cardiac insufficiency;
- •Hypertension, which is uncontrolled by the drug, is defined as: systolic blood pressure ≥ 160 mmHg, or diastolic blood pressure ≥ 100 mmHg;
- •Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
- •Surgery (<28 days) before the study was selected or the surgical incision did not completely heal, or there were other unhealed wounds;
- •Active or uncontrolled serious infections;
- •Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
- •Increasing the risk associated with participating in a study or study drug, and at the discretion of the investigator, may lead to other conditions in which the patient is not eligible for inclusion in the study.
研究组 & 干预措施
Anlotinib plus Platinum-based chemotherapy
- Take anlotinib hydrochloride 12mg once daily for two weeks, stop for one week, the program repeats every 21 days for 2 cycles.
- Platinum-based chemotherapy regimens for neoadjuvant:(1)Carboplatin was given dosed to an area under the serum concentration-time curve (AUC) of 6 i.v. injection on day 1, paclitaxel was given 150 mg/m^2 i.v. on day 1, every 21 days for 2 cycles.Or(2) Carboplatin was given dosed to an AUC 5 or Cisplatin was given 75 mg/m^2 ,i.v. on day 1, pemetrexed was given 500 mg/m^2 i.v. on day 1 for nonsquamous, every 21 days for 2 cycles.Or(3) Cisplatin was given 75 mg/m^2 i.v. on day 1; docetaxel was given 75 mg/m^2 i.v. on day 1 ,each 21-day cycle for 2 cycles.
干预措施: Anlotinib hydrochloride (Drug)
platinum-based chemotherapy
Platinum-based chemotherapy regimens for neoadjuvant:(1)Carboplatin was given dosed to an AUC of 6 i.v. injection on day 1, paclitaxel was given 150 mg/m^2 i.v. on day 1, every 21 days for 2 cycles.Or(2) Carboplatin was given dosed to an AUC 5 or Cisplatin was given 75 mg/m^2 ,i.v. on day 1, pemetrexed was given 500 mg/m^2 i.v. on day 1 for nonsquamous, every 21 days for 2 cycles.Or(3) Cisplatin was given 75 mg/m^2 i.v. on day 1; docetaxel was given 75 mg/m^2 i.v. on day 1 ,each 21-day cycle for 2 cycles.
干预措施: platinum-based chemotherapy medicine (Drug)
结局指标
主要结局
Lymph node(N2)downstage rate
时间窗: 3 months
Lymph node downstage rate is depended on the image or pathology dignosis after surgery,staging from N2 to N1 / N0.
次要结局
- Objective Response Rate (ORR)(3 months)
- Resectability rate(Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization.)
- Pathological complete response (pCR) rate(3 months)
- adverse events(AEs)(3 months)
- Disease-free Survival （DFS）(Every 3 months.)
- Overall Survival (OS)(3 years)
研究者
Jiexia Zhang
Clinical Professor
The First Affiliated Hospital of Guangzhou Medical University