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

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

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.

Study Overview

• Status: Unknown
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Anlotinib; Drug: Topotecan; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 184
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yuankai Shi, Master; Phone Number: 010-87788293; Email: syuankaipumc@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100083
      • Beijing Cancer Hospital
      • Contact: Ziping Wang, Doctor; Phone Number: 010-88196456; Email: wangzp2007@126.com
    • Beijing, Beijing, China, 100083
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Yuankai Shi, Master; Phone Number: 010-87788293; Email: syuankaipumc@126.com
      • Principal Investigator: Yuankai Shi, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Small cell lung cancer patients.
2. The clinical stage at baseline is extensive.
3. A measurable lesion.
4. Disease progression.
5. ≥ 18 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
6. Adequate laboratory indicators.
7. No pregnant or breastfeeding women, and a negative pregnancy test.
8. Understood and signed an informed consent form.

Exclusion Criteria:

1. Has used topotecan and anlotinib hydrochloride capsules.
2. Has used other anti-angiogenic drugs and immunologically targeted drugs.
3. Has other malignant tumors within 5 years.
4. Symptomatic brain metastasis.
5. Has a variety of factors affecting oral medications.
6. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage.
7. Spinal cord compression.
8. Has received radiotherapy, chemotherapy, surgery less than 4 weeks before randomization.
9. Adverse events caused by previous treatment did not recover to grade 1.
10. Has received major surgical treatment within 4 weeks before randomization.
11. Arteriovenous thrombosis occurred within 6 months.
12. Has drug abuse history that unable to abstain from or mental disorders.
13. Has severe or uncontrolled disease.
14. Participated in other clinical trials within 4 weeks.
15. Tumor invades the large blood vessels.
16. Daily hemoptysis ≥2.5 mL within 1 month before the first dose.
17. According to the investigators' judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; 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; A multi-target receptor tyrosine kinase inhibitor.; Drug: Topotecan; A topoisomerase I inhibitor.
PLACEBO_COMPARATOR: Placebo group; 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: Topotecan; A topoisomerase I inhibitor.; Drug: Placebos; Anlotinib blank analog capsule.

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

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 31, 2019
• Primary Completion (ANTICIPATED): July 31, 2021
• Study Completion (ANTICIPATED): July 31, 2022

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (ACTUAL): August 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: ALTN-12-III-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No