Clinical trial NCT03703596: Anlotinib Versus Docetaxel as the Second-line Treatment in EGFR Wild Type Patients With Advanced NSCLC
Official title: Efficacy and Safety of Anlotinib Versus Docetaxel in Advanved Non-squamous Non-small-cell Lung Cancer Without EGFR Mutation Who Failed in First-line Platinum-based Doublet Chemotherapy: an Open, Muti-center, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Cancer
Lung Cancer Metastatic
Lead sponsor: Sichuan Cancer Hospital and Research Institute
Sponsor class: OTHER
Collaborators: name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
First posted: 2018-10-12
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Objective response rate(ORR)
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Deyang
country: China
facility: People's hospital of deyang city
state: Sichuan
city: Chengdu
country: China
facility: Chengdu fifth people's hospital
city: Chengdu
country: China
facility: Sichuan cancer hospital
city: Guangan
country: China
facility: People's hospital of guangan city
city: Luzhou
country: China
facility: The affiliated hospital of southwest medical university
city: Nanchong
country: China
facility: Nanchong central hospital
city: Neijiang
country: China
facility: Neijing second people's hospital
city: Suning
country: China
facility: Suning central hospital
city: Zigong
country: China
facility: Zigong first people's hospital
city: Zigong
country: China
facility: Zigong fourth people's hospital
Study officials:
affiliation: Director of Medical Oncology Thoracic Department
name: Wenxiu Yao, PhD
role: PRINCIPAL_INVESTIGATOR
References: