Study of Anlotinib Hydrochloride Capsule in Subjects With Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor-associated kinases involved in cell proliferation such as PDGFRα/β, c-Kit, and Ret have significant inhibitory activities.

Official Title
-----------------
A Randomized, Double-Blind, Multicenter, Phase Ⅲ Study of Anlotinib Hydrochloride Capsule Combined With Topotecan Versus Placebo Combined With Topotecan in Subjects With Small Cell Lung Cancer

Conditions
-----------------
Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Anlotinib
* Drug: Placebos
* Drug: Topotecan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Small cell lung cancer patients. The clinical stage at baseline is extensive. A measurable lesion. Disease progression. ≥ 18 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months. Adequate laboratory indicators. No pregnant or breastfeeding women, and a negative pregnancy test. Understood and signed an informed consent form. Exclusion Criteria: Has used topotecan and anlotinib hydrochloride capsules. Has used other anti-angiogenic drugs and immunologically targeted drugs. Has other malignant tumors within 5 years. Symptomatic brain metastasis. Has a variety of factors affecting oral medications. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage. Spinal cord compression. Has received radiotherapy, chemotherapy, surgery less than 4 weeks before randomization. Adverse events caused by previous treatment did not recover to grade 1. Has received major surgical treatment within 4 weeks before randomization. Arteriovenous thrombosis occurred within 6 months. Has drug abuse history that unable to abstain from or mental disorders. Has severe or uncontrolled disease. Participated in other clinical trials within 4 weeks. Tumor invades the large blood vessels. Daily hemoptysis ≥2.5 mL within 1 month before the first dose. According to the investigators' judgement.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Experimental group<br>Anlotinib hydrochloride capsules given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) and topotecan 1.5mg/m2 IV d1-5. | Drug: Anlotinib<br>* A multi-target receptor tyrosine kinase inhibitor.<br>Drug: Topotecan<br>* A topoisomerase I inhibitor.<br>|
| Placebo Comparator: Placebo group<br>Anlotinib hydrochloride placebo given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) and topotecan 1.5mg/m2 IV d1-5. | Drug: Placebos<br>* Anlotinib blank analog capsule.<br>Drug: Topotecan<br>* A topoisomerase I inhibitor.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) evaluated by IRC | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause; IRC defined as Independent Review Committee. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) evaluated by investigator | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause. | up to 24 months | 
| Overall survival (OS) | OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. | up to 24 months | 
| Overall Response Rate (ORR) | Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR). | up to 24 months | 
| Disease Control Rate (DCR) | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 24 months | 
| Duration of Overall Response (DOR) | The time when the patient first achieved complete or partial remission to disease progression. | up to 24 months | 
| PFS rate at month 6 | The percentage of PFS at month 6. | up to 6 months | 
| OS rate at month 6 | The percentage of OS at month 6. | up to 6 months | 
| OS rate at month 12 | The percentage of OS at month 12. | up to 12 months | 
| The efficacy of intracranial lesions | To evaluate the efficacy of of intracranial lesions. | up to 24 months | 
| Adverse Event (AE) | Safety data | up to 24 months | 
| Serious Adverse Event (SAE) | Safety data | up to 24 months | 
| Abnormal laboratory test index | Safety data | up to 24 months |