Anlotinib Versus Docetaxel as the Second-line Treatment in EGFR Wild Type Patients With Advanced NSCLC

NCT ID: NCT03703596

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-16
• Study Completion Date: 2020-11-01

Brief Summary

This study is conducted to explore the safety and efficacy of anlotinib, a tyrosine kinase inhibitors of Vascular Endothelial Growth Factor Receptor 2（VEGFR）、FGFR（Fibroblast Growth Factor Receptor）, Platelet-derived growth factor Receptor（PDGFR） and c-kit, vs docetaxel in advanced Non-squamous Non-small cell lung cancer harbouring wild-type epidermal growth factor receptor (EGFR) .

Detailed Description

This is a multicentre randomised controlled clinical trial conducted in China to compare the efficacy and and safety of Anlotinib vs Docetaxel in patients of EGFR mutation-negative advanced nonsquamous non-small Cell Lung Cancer.

Eligible patients will be randomized to arm A and arm B:

Arm A: Patients on the anlotinib arm received 12mg anlotinib orally daily on day 1 to 14 of a 21-day cycle.

Arm B: Patients on the docetaxel arm received 75mg/m2 docetaxel as intravenous infusion on day 1 of a 21-day cycle.

Conditions

Lung Cancer; Lung Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anlotinib hydrochloric

Anlotinib (12mg QD PO d1-14, 21 days per cycle)

Group Type: EXPERIMENTAL

Anlotinib Hydrochloride

Intervention Type: DRUG

Anlotinib (12mg QD PO d1-14, 21 days per cycle)

Docetaxel

Docetaxel (75mg/m2 IV d1, 21 days per cycle)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel (75mg/m2 IV d1, 21 days per cycle)

Interventions

Anlotinib Hydrochloride

Anlotinib (12mg QD PO d1-14, 21 days per cycle)

Intervention Type: DRUG

Docetaxel

Docetaxel (75mg/m2 IV d1, 21 days per cycle)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• -≥ 18 and ≤ 70 years of age. Signed the informed consent form prior to patient entry
• Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV .
• Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV .
• Patients who has failed from the first-line Platinum-based Doublet chemotherapy harbouring epidermal growth factor receptor(EGFR) sensitive mutations negetive, confirmed by pathological or blood test results) ）,ALK/ROS1 mutation-negative or unknown (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment） Noted: failed from prior treatment means(1) progress disease confirmed by CT; cannot tolerable from standard treatment, such as hematologic toxicities ≥ level 4; non-hematologic toxicities ≥ level 3;damages of heart/liver/kidney ≥ level 2 in CTC AE 4.0
• Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI；prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
• Life expectancy ≥3 months.
• Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
• Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0) , except alopecia;
• The blood routine examination need to be standard (no blood transfusion and blood products within 14 days, no g-csf and other hematopoietic stimulating factor correction); Hemoglobin（HB）≥90 g/L; A Neutrophil count of （ANC）≥1.5×10e9/L; A Platelet count of （PLT）≥80×10e9/L; A Total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); A alanine aminotransferase (ALT) and a aspartate aminotransferase (AST) of ≤2.5 UNL, in case of liver metastasis ALAT and ASAT≤5 UNL; A creatinine (Cr) of ≤1.5 UNL; a creatinine clearance rate ≥ 60ml/min (Cockcroft-Gault);
• The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 8 weeks after it 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 8 weeks Voluntarily joined the study and signed informed consent, with good compliance and follow-up.

Exclusion Criteria

• -Mixed Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer, adenocarcinoma mixed with squamous cell carcinoma
• No squamous NSCLC with hemoptysis (>50ml/day);
• Treated by taxel or similar drugs in 12months;
• symptoms of brain metastases cannot be controlled and treated within less than 2 months
• Tumor locate within a distance of less than 5 mm from the large vessels, less than 2 cm from the bronchial tree, or has invaded local large vessels; tumor with cavum or necrotic obviously;
• Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg, despite optimal drug therapy).
• Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms); according to NYHA standard, grade Ⅲ ~ Ⅳ heart failure, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) <50%.
• Coagulation dysfunction (INR> 1.5, PT> ULN +4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment;note: Note: under the premise of International Normalized ratio (INR) of prothrombin time (PT) Less than or equal to 1.5, allow to administrate low-dose heparin (adult daily dose is 06000 ~ 12000 U) or low-dose aspirin (100 mg daily dosage or less) , for prophylactic purposes
• Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.
• Patients whose has peripheral neuropathy over level 2 in CTC AE4.0, except trauma.
• Patients with respiratory syndrome (difficulty breathing of level 2 or higher ), serous cavity effusion need to surgical treatment ( including pleural of level 2 or higher with respiratory distress and anoxia
• Patients who have unhealed wounds or fractures for a long time.
• Patients with severe infections , and need to receive systemic antibiotic treatment
• Decompensated diabetes or other contraindication with high dose glucocorticoid therapy;
• Cirrhosis or decompensated liver disease; active or untreated hepatitis C and/or Hepatitis B virus (HBV) infection（prior hepatitis B history, HBsAg positive and HBV DNA≥500IU/mL; HCV RNA positive and hepatic Insufficiency
• Has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc
• Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening.
• Severe weight loss (> 10%) Within 6 weeks before Random
• Patients who had obvious hemoptysis (>50ml/day) within 3 months before screening; Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc;
• Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.
• Allergic reactions to anotol or excipients in experimental drugs.
• Allergic reactions to contrast medium
• Patients have participated in other antitumor drug clinical trials Within 4 weeks before enrollment or prepare to receive systemic anti-tumor treatment during the study or Within 4 weeks before randomization
• Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sichuan Cancer Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Jianing Tang

assistant of Medical Oncology Thoracic Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wenxiu Yao, PhD

Role: PRINCIPAL_INVESTIGATOR

Director of Medical Oncology Thoracic Department

Locations

People's hospital of deyang city

Deyang, Sichuan, China

Chengdu fifth people's hospital

Chengdu, , China

Sichuan cancer hospital

Chengdu, , China

People's hospital of guangan city

Guangan, , China

The affiliated hospital of southwest medical university

Luzhou, , China

Nanchong central hospital

Nanchong, , China

Neijing second people's hospital

Neijiang, , China

Suning central hospital

Suning, , China

Zigong first people's hospital

Zigong, , China

Zigong fourth people's hospital

Zigong, , China

Countries

China

Central Contacts

Wenxiu Yao, PhD

Role: CONTACT

ywxhlx@sina.com

+8618908178836

Jianning Tang

Role: CONTACT

+8618328581906

Facility Contacts

Xin Ye

Role: primary

lang he

Role: primary

jing liang

Role: primary

scchgcp@163.com

+86028-85420509

xingyuan wang

Role: primary

sheng lin

Role: primary

xin hu

Role: primary

ou jiang

Role: primary

jun yan

Role: primary

jidong miao

Role: primary

Other Identifiers

ALTER-L023

Identifier Type: -

Identifier Source: org_study_id