Study of Anlotinib as the Maintenance Therapy for Extensive-stage Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
Anlotinib has been approved as a third-line treatment for advanced non-small-cell lung cancer. A phase II clinical studies of small cell lung cancer (ALTER-1210) also showed that, compared with placebo, Anlotinib could improve the patients survival and had less toxic side effects after 2-3 line therapy. The purpose of this multicenter, randomized, prospective study is to investigate the efficacy and safety of Anlotinib as the maintenance therapy for Extensive-stage small cell lung cancer after combined with etoposide and cisplatin chemotherapy.

Official Title
-----------------
A Randomized Controlled Multicenter Clinical Trial to Compare the Efficacy and Safety of Anlotinib as the Maintenance Therapy for Extensive-stage Small Cell Lung Cancer After Combined With Etoposide and Cisplatin Chemotherapy

Conditions
-----------------
Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Anlotinib Hydrochloride; etoposide and cisplatin
* Drug: etoposide and cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic or cytologic diagnosis of small cell lung caner Advanced small cell lung cancer who had no prior cisplatin-based chemotherapy or radiotherapy,at least one measurable lesion (by RECIST1.1) Males or females between 18 Years to 75 Years. Performance status of 0～2 on the ECOG criteria. Main organs function is normal Expected survival is above three months. with asymptomatic brain metastases. At least one measurable lung tumor lesion (according to RECIST criteria, the application of conventional technology, diameter length of the lesion >= 20mm or spiral CT >=10mm). Adequate hematologic (Leukocyte count >= 4.0×109/L, neutrophil count>=2.0×109/L, hemoglobin>=95g/L, platelets>=100×109/L), hepatic function (aspartate transaminase (AST) & alanine transaminase(ALT) =<upper normal limit(UNL) x1.5, bilirubin level =< UNL x 1.5). Patient can take oral medicine. Patients have the ability to understand and voluntarily sign the informed consent, and allow adequate follow-up. Exclusion Criteria: History of cardiovascular disease: congestive heart failure (CHF) > New York Heart Association (NYHA) II, active coronary artery disease(patients with myocardial infarction six months ago can be recruited), arrhythmias need to be treated (allow taking beta blockers or digoxin). Serious clinical infection (> NCI-CTCAE version 4.0 ,infection standard II). Patients with epilepsy who need to take medicine (such as steroids or anti epilepsy agents). The patients had accepted allogeneic organ transplantation. Bleeding tendency or coagulation disorders. patients who need renal dialysis. suffered from other tumor within 5 years( Except: cervical carcinoma in situ, cured basal cell carcinoma, cured bladder epithelial tumor). uncontrolled hypertension (systolic pressure>150 mmHg , or diastolic pressure> 90 mmHg). thrombosis or embolism(cerebrovascular accidents including transient ischemic attack within the last 6 months). pulmonary hemorrhage >CTCAE grade 2 within 4 weeks before first use of drugs. Other organ hemorrhage >CTCAE grade 3 within 4 weeks before first use of drugs. severe uncured wounds, ulcers or fracture. uncured dehydration. Drugs abuse and medical, psychological or social conditions may interfere with the patient's participation in research or the results of the evaluation effect. Patients are allergic to drugs used in research. Factors influencing the safety and compliance of patients. Inability to comply with protocol or study procedures. Pregnant or breast-feeding. The researcher believe that the Patient is not suitable to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib + Chemotherapy<br>Patients receive etoposide 100mg/m2 from day 1 to day 3, cisplatin 75mg/m2 on day 1, and Anlotinib 12mg/d on day 1 to day 14 , repeated every 21 days, a total of 4-6 cycles, and then continue to take Anlotinib 12mg/d on day 1 to day 14, repeated every 21 days until progressive Disease(PD). | Drug: Anlotinib Hydrochloride; etoposide and cisplatin<br>* etoposide 100mg/m2 from day 1 to day 3, cisplatin 80mg/m2 on day 1 and Anlotinib Day 1 to day 14 followed by 7 days off treatment in a 21-day cycle, repeated every 21 days<br>|
| Placebo Comparator: Chemotherapy<br>Patients receive etoposide 100mg/m2 from day 1 to day 3, cisplatin 75mg/m2 on day 1, repeated every 21 days, a total of 4-6 cycles, and then follow up observation until PD. | Drug: etoposide and cisplatin<br>* etoposide 100mg/m2 from day 1 to day 3, cisplatin 80mg/m2 on day 1, repeated every 21 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The first day of treatment to the date that disease progression is reported | From randomization，each 42 days up to PD or death(up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The first day of treatment to death or last survival confirm date | From randomization until death (up to 5 years) | 
| Objective Response Rate |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Treatment-related adverse events | Treatment-related adverse events are assessed by common terminology criteria for adverse events(CTCAE) V4.0. | the first date of treatment to 30 days after the last dose of study drug,assessed up to 24 months | 
| Performance Status | Performance Status of patients will be assessed by Zubrod-Eastern cooperative oncology group(ECOG)-world health organization(WHO). | the first date of treatment to 30 days after the last dose of study drug, assessed up to 24 months | 
| Disease Control Rate |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Small Cell Lung Cancer; Anlotinib; Maintenance therapy