Irinotecan Liposome Combined With Anlotinib as Second-line Regimen for SCLC

This study is a single arm, multi-center, prospective clinical trial. The purpose of this study is to evaluate the efficacy and safety of liposomal irinotecan combined with anlotinib hydrochloride for relapsed small-cell lung cancer, who have progressed on or less than 6 month after platinum-based first-line therapy.

Patients will receive irinotecan liposome injection at 70 mg/m\^2 intravenously, on Days 1 of every 14-day cycle and anlotinib (12 mg/day) for 2 consecutive weeks and then discontinued for 1 week. The treatment is continued until disease progression or intolerable toxicity.

Eligibility Criteria:
Inclusion Criteria:

* 1) Aged ≥18 and ≤75 years old;
* 2) Histologically or cytologically confirmed small cell lung cancer;
* 3) At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1;
* 4) Radiologically confirmed recurrence or progression within 6months after platinum-based, first-line chemotherapy or chemoradiation therapy;
* 5) Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
* 6) Expected survival of more than 3 months;
* 7) Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other anti-neoplastic therapy (recovered to no more than Grade 1 of CTCAE 5.0 criteria or baseline, with the exception of alopecia or other toxicity without safety concerns by the investigators' judgment);
* 8) Adequate major organ function, patients should meet the following criteria:

  ① Bone marrow function: absolute neutrophile count (ANC)≥1.5×109/L，platelet (PLT)≥100×109/L, hemoglobin (Hb)≥90g/L, white blood cell (WBC)≥3.0×109/L；

  ② Hepatic function: total bilirubin≤1.5×upper limit of normal value(ULN)；ALT and AST≤2.5×ULN，liver metastasis：≤5×ULN；

  ③ Renal function: serum creatinine ≤1.5×ULN and creatinine clearance rate ≥60 mL/min;

  ④ Coagulation function：Activated partial thromboplastin time(APTT)、International normalized ratio(INR)、prothrombin time (PT)≤1.5×ULN；

  ⑤ urine routines show urine protein \< 2+(when urine protein \>2+, urine protein quantity\< 1.0 g during 24 hours before 7 days);
* 9) Patients fully understood and volunteered to participate in the study.

Exclusion Criteria:

* 1) Patients with large cell neuroendocrine lung carcinoma or combined small cell lung carcinoma;
* 2) Patients with asymptomatic central nervous system (CNS) metastases prior to enrollment or those who have CNS disease requiring increase in the dose of steroid. (Patients with controlled CNS metastasis can participate in the trial);
* 3) Patients with uncontrolled pleural effusion, abdominal effusion and pericardial effusion after repeated drainage or other treatment within 2 weeks prior to the first dose of this study, and those judged by the clinicians to be unsuitable for the study;
* 4) Diagnosed with any other cancer within the past 5 years (except for cured basal cell carcinoma and in situ cancer);
* 5) Patients who have received prior irinotecan/ liposomal irinotecan and anti-angiogenic drugs such as anlotinib and bevacizumab , etc.
* 6) Concomitant use of strong CYP3A4 inducers within 2 weeks or strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week of the first dose of the study drug;
* 7) Patients who have received other anti-tumor treatments(including radiotherapy, chemotherapy, immunotherapy, etc.) within 4 weeks before the first dose;
* 8) Combined with uncontrolled systemic diseases, including unstable angina, myocardial infarction, congestive heart failure, severe ventricular arrhythmia , etc.
* 9) Severe pulmonary disease within 6 months prior to enrolment, such as interstitial pneumonia, pulmonary fibrosis, radiation induced pneumonitis requiring steroid therapy, and other moderate and severe lung diseases which affect lung function;
* 10) Arterial/venous thrombosis within 6 months prior to enrollment, e.g. cerebrovascular accident (include temporary ischemic attack), deep venous thrombosis, pulmonary embolism.
* 11) Symptoms or propensity to bleed within 3 months prior to screening (include gastrointestinal hemorrhage, ulcerative gastric bleeding, fecal occult blood 2+ or above, vasculitis);
* 12) Patients had undergone major surgical procedure(except for diagnostic surgery) within 4 weeks before dosing or was scheduled to receive major procedure during the study;
* 13) unhealed wounds, ulcers or fractures;
* 14) Imaging showed tumors have involved important blood vessels or by investigators determine likely during the follow-up study and cause fatal hemorrhage;
* 15) Active and uncontrolled bacterial, viral, fungal infection requiring systemic treatment;
* 16) Active hepatitis B/C, or HIV infection;
* 17) Known intolerance or allergy to therapeutic drugs and their excipients;
* 18) Clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea \> grade 1;
* 19) Pregnant or breast feeding;
* 20) Patient is not suitable for the study in the investigator's opinion.