Clinical trial NCT04181372: A Study of Neoadjuvant Chemotherapy Plus Anlotinib in Stage III(N2) Non-small-cell Lung Cancer
Official title: A Phase II Study of Neoadjuvant Double-drug Chemotherapy With Platinum Plus Anlotinib Hydrochloride in Stage III(N2) Non-small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stage III Non-small-cell Lung Cancer
Keywords: Stage III Non-small-cell Lung Cancer
Anlotinib Hydrochloride
Neoadjuvant
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Age :18 Years to 75 Years (Adult, Older Adult)
2. Pathological diagnosis with Stage III-N2 NSCLC which is clinically resectable and the N2 is diagnosed by either mediastinoscopy,EBUS,PET/CT;
3. EGFR、ALK、ROS1 mutation-negative；Patients with squamous cell carcinoma may not have genetic testing;PD-L1\<5%;
4. According to the RECIST 1.1 standard, there is at least one measurable target lesion;
5. ECOG physical score 0-1 points; expected survival time ≥ 3 months;
6. 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;
7. Subjects voluntarily joined the study and signed informed consent, with good adherence and follow-up.

Exclusion Criteria:

1. Stage I, II , IV orNSCLC;
2. 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;
3. Patients with contraindication of chemotherapy
4. Subjects who have previously used Anlotinib;
5. 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;
6. 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;
7. 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;
8. A thrombotic event occurs within 6 months (including arteriovenous thrombosis, pulmonary embolism, cerebrovascular accident, including transient ischemic attack, etc.);
9. 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;
10. Hypertension, which is uncontrolled by the drug, is defined as: systolic blood pressure ≥ 160 mmHg, or diastolic blood pressure ≥ 100 mmHg;
11. 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;
12. Surgery (\<28 days) before the study was selected or the surgical incision did not completely heal, or there were other unhealed wounds;
13. Active or uncontrolled serious infections;
14. Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
15. 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.

Primary outcomes:
measure: Lymph node(N2)downstage rate
timeFrame: 3 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 3 months
measure: Resectability rate
timeFrame: Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization.
measure: Pathological complete response (pCR) rate
timeFrame: 3 months
measure: Disease-free Survival （DFS）
timeFrame: Every 3 months.
measure: Overall Survival (OS)
timeFrame: 3 years
measure: adverse events(AEs)
timeFrame: 3 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Jiexia Zhang, prof.
role: STUDY_CHAIR
References: