Clinical trial NCT02388919: Study of Anlotinib in Patients With Advanced Non-small Cell Lung Cancer（ALTER0303）
Official title: A Registered Randomized, Double-Blind, Placebo-Controlled (2:1), Multi-Centered Clinical Trial of Anlotinib as a Treatment for Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: anlotinib
Cancer
NSCLC
Non-small Cell Lung Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 439
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy and safety of Anlotinib as the 3-line treatment of patients with advanced non-small lung cancer, with placebo control.

Detailed description: Anlotinib (AL3818) is a kind of innovative medicines approved by State Food and Drug Administration（SFDA:2011L00661） which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent
2. Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, with measurable nidus(using RECIST 1.1)
3. at least two systematic chemotherapy with upwards of 3-line treatments or cannot suffer
4. Patients must provide detectable specimen (from tumor tissue or hydrothorax) before participating, who negative in EGFR\&ALK can participate or who positive in EGFR\&ALK, have or have not drug tolerance after the treatment with relative targeted drugs
5. ECOG PS：0-1,Expected Survival Time: Over 3 months
6. main organs function is normal
7. The woman patients of childbearing age who must agree to take contraceptive methods (e.g. intrauterine device, contraceptive pill or condom) during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; The man patients who must agree to take contraceptive methods during the research and within another 6 months after it

Exclusion Criteria:

1. have used Anlotinib before
2. Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
3. examined as positive in EGFR\&ALK mutation detection and never take the treatment of TKIs
4. central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (\>50ml/day)
5. other kinds of malignancies within 5 years or for now
6. plan to take systemic anti-tumor therapy within 4 weeks before grouping or during the medicine-taking period of this research, including Cytotoxic Therapy, Signal Transduction Inhibitor, and Immunotherapy (or who use Mitomycin C within 6 weeks before taking the treatment with experimental drug); The patients who have already taken Extended Field Radiotherapy (EF-RT) within 4 weeks before grouping or Limited Field Radiotherapy with proposed assessment of nidus within 2 weeks before grouping
7. have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included
8. with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus)
9. pleural effusion or ascites, resulting in respiratory syndrome (≥CTC AE level 2)
10. symptoms of brain metastases cannot be controlled and treated within less than 2 months
11. get any severe diseases or the ones that cannot be controlled
12. take major surgical treatments, open biopsy, or get overt traumatic injury within 28 days before grouping
13. have any habitus or medical history of hemorrhage, however severe it is; the patients who have non healing wounds, ulcer or fracture after any events with hemorrhage or bleeding (≥CTCAE level 3)
14. get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), deevenous thrombosis, and pulmonary embolism
15. ever abuse psychiatric drugs and cannot abstain or who are diagnosed with mental disorder
16. have participated in other clinical trials of anti-tumor medicine within 4 weeks
17. diagnosed with disease which will severely endanger the security of patients or influence the completion of this research.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 24 months)
Secondary outcomes:
measure: Progress free survival (PFS)
timeFrame: each 42 days up to PD or death(up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Until 30 day safety follow-up visit
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Capital Medical University, Beijing Chest Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: Xinqiao Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Province Tumor Hospital
state: Fujian
city: Lanzhou
country: China
facility: Gansu Province Tumor Hospital
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial People 's Hospital
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou Military General Hospital
state: Gansu
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shantou
country: China
facility: First Affiliated Hospital of Shantou University Medical College
state: Guangdong
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin medical university affiliated tumor hospita
state: Heilongjiang
city: Luoyan
country: China
facility: Henan Province Tumor Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Province Tumor Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Lianyungang
country: China
facility: Lianyungang First People 's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Medical College Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Province Tumor Hospital
state: Jiangxi
city: Nanchang
country: China
facility: Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Province Tumor Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning Provincial Tumor Hospital
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital，Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Province Tumor Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi City Tumor Hospita
state: Shandong
city: Shanghai
country: China
facility: Chest hospital affiliated to Shanghai jiaotong university
state: Shanghai
city: Shanghai
country: China
facility: Cancer Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xinhua hospital affiliated to Shanghai jiaotong university
state: Shanghai
city: Xian
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Xian
country: China
facility: Tang Du Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital , Sichuan University
state: Sichuan
city: Chongqing
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Tianjin
country: China
facility: 20th Floor, Block C, Lake Road, Hexi District, Tianjin Medical University Cancer Institute and Hospital .
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Province Tumor Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Province Tumor Hospital
state: Zhejiang
Study officials:
affiliation: Chest hospital affiliated to Shanghai jiaotong university
name: Baohui Han, professor
role: STUDY_DIRECTOR
affiliation: Tianjin Medical University Cancer Hospital
name: Kai Lee, professor
role: STUDY_DIRECTOR
References:
citation: Qin T, Liu Z, Wang J, Xia J, Liu S, Jia Y, Liu H, Li K. Anlotinib suppresses lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma through a process potentially involving VEGFR-3 signaling. Cancer Biol Med. 2020 Aug 15;17(3):753-767. doi: 10.20892/j.issn.2095-3941.2020.0024.
citation: Jiang S, Liang H, Liu Z, Zhao S, Liu J, Xie Z, Wang W, Zhang Y, Han B, He J, Liang W. The Impact of Anlotinib on Brain Metastases of Non-Small Cell Lung Cancer: Post Hoc Analysis of a Phase III Randomized Control Trial (ALTER0303). Oncologist. 2020 May;25(5):e870-e874. doi: 10.1634/theoncologist.2019-0838. Epub 2020 Feb 20.
citation: Zhang PL, Liu ZJ. Esophago-tracheobronchial fistula following treatment of anlotinib in advanced squamous cell lung cancer: Two case reports. Medicine (Baltimore). 2019 Nov;98(44):e17700. doi: 10.1097/MD.0000000000017700.
citation: Si XY, Wang HP, Zhang XT, Wang MZ, Zhang L. [Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer]. Zhonghua Nei Ke Za Zhi. 2018 Nov 1;57(11):830-834. doi: 10.3760/cma.j.issn.0578-1426.2018.11.007. Chinese.
citation: Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039.
citation: Si X, Zhang L, Wang H, Zhang X, Wang M, Han B, Li K, Wang Q, Shi J, Wang Z, Cheng Y, He J, Shi Y, Chen W, Wang X, Luo Y, Nan K, Jin F, Li B, Chen Y, Zhou J, Wang D. Quality of life results from a randomized, double-blinded, placebo-controlled, multi-center phase III trial of anlotinib in patients with advanced non-small cell lung cancer. Lung Cancer. 2018 Aug;122:32-37. doi: 10.1016/j.lungcan.2018.05.013. Epub 2018 May 18.