Anlotinib Plus Docetaxel for the Treatment of EGFR/ALK/ROS1 Mutation-negative Advanced Nonsquamous NSCLC

Anlotinib Plus Docetaxel Versus Docetaxel for Treatment of EGFR/ALK/ROS1 Mutation-negative Advanced Nonsquamous NSCLC After Disease Progression on Platinum-based Therapy : a Multicentre, Double-blind, Randomised Explorative Trial

Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development. It can inhibit the angiogenesis related kinase, such as VEGFR, FGFR, PDGFR, and tumor cell proliferation related kinase -c-Kit kinase. In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months. Therefore,we envisage using anlotinib plus docetaxel treat the EGFR/ALK/ROS1 mutation-negative advanced nonsquamous Non-small cell lung cancer patients who were failure in the treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS or OS.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Anlotinib Plus Docetaxel; Drug: Docetaxel

Detailed Description

This is a multicentre randomised controlled clinical trial conducted in China to compare the effectiveness and safety of Anlotinib Plus Docetaxel in patients of EGFR/ALK/ROS1 mutation-negative Advanced nonsquamous Non-squamous Non-small Cell Lung Cancer.

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

Arm A: Patients on the anlotinib and docetaxel arm received 75mg/m2 docetaxel as intravenous infusion on day 1 of a 21-day cycle and 12mg anlotinib orally daily on day 1to 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.

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed and dated informed consent
• diagnosed with non squamous advanced NSCLC (phase IIIB/IIIC/IV) through pathology,with measurable nidus(using RECIST 1.1)
• have failed for platinum two drugs chemotherapy
• EGFR/ALK/ROS1 mutation-negative
• ECOG PS：0-1,Expected Survival Time: Over 3 months
• main organs function is normal
• 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 2 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 2 months after it

Exclusion Criteria:

• Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
• squamous non small cell lung cancer （including adenosine squamous cell carcinoma ）
• have not used docetaxel before（except adjunctive therapy）
• iconography (CT or MRI) shows that the tumor vessels have 5 mm or less, or Cardiovascular involvement by Central tumor ; Or obvious lung empty or necrotic tumor
• patients with brain or central nervous system metastases, including leptomeningeal disease, or CT/MRI examination revealed brain or leptomeningeal disease） (28 days before the random treatment has been completed and the symptoms of patients with brain metastases from stable can into the group, but need to the cerebral MRI, CT or vein angiography confirmed as without symptoms of cerebral hemorrhage)
• patients are participating in other clinical studies less than 4 weeks from the end of a previous clinical study
• other kinds of malignancies within 5 years or for now
• have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included
• abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT ULN > 1.5), with bleeding tendency or be treated with thrombolysis and anticoagulation
• urine routines show urine protein≥ ++, or urine protein quantity≥ 1.0 g during 24 hours
• uncontrollable hypertensive (systolic blood pressure or greater 160 mmHg or diastolic blood pressure or greater 90 mmHg, despite the best drug treatment)
• the effects of surgery or trauma had been eliminated for less than 14 days before admission to the study group
• patients with severe infections , and need to receive Systemic antibiotic treatment
• significant cardiac disease as defined as: grade II or greater myocardial infarction, unstable arrhythmia(Including corrected QT interval (QTc )period between male or greater 450 ms, female or greater 470 ms); New York Heart Association (NYHA) grade II or greater heart dysfunction , or Echocardiography reveal left ventricular ejection fraction （LVEF）Less than 50%
• patients with NCI-CTCAE grade II or greater peripheral neuropathy, except due to trauma
• pleural effusion or ascites, resulting in respiratory syndrome (≥CTC AE level 2)
• serious, non-healing wound, ulcer, or bone fracture
• decompensated diabetes or high dose glucocorticoid treatment of other contraindication
• has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc
• has Clinically significant hemoptysis Within 3 months before Random (daily hemoptysis than 50 ml;Or significant clinical significance of bleeding symptoms or have definite bleeding tendency, such as gastrointestinal bleeding, bleeding ulcers, baseline period + + and above of fecal occult blood, or vasculitis, etc
• has venous thromboembolism events Within 6 months before Random, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc
• whole body antitumor treatment was planned in the first 4 weeks(except diphosphonate) or during this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy， Chinese medicine with antitumor effect. Field scale radiotherapy (EF-RT) within 4 weeks before grouping or limited field radiotherapy before grouping were carried out in 2 weeks ;
• a known history of HIV testing positive or acquired immunodeficiency syndrome (AIDS)
• untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA more than 1 x 103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal); Combined with hepatitis b and hepatitis c infection
• serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib Plus Docetaxel; Anlotinib (12mg QD PO d1-14, 21 days per cycle) and Docetaxel (75mg/m2 IV d1)	Drug: Anlotinib Plus Docetaxel; Anlotinib (12mg QD PO d1-14, 21 days per cycle) and Docetaxel (75mg/m2 IV d1)
Active Comparator: Docetaxel; Docetaxel (75mg/m2 IV d1)	Drug: Docetaxel; Docetaxel (75mg/m2 IV d1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progress free survival	each 42 days up to PD or death(up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	From randomization until death (up to 24 months)
ORR	Objective Response Rate	each 42 days up to intolerance the toxicity or PD (up to 24 months)
DCR	Disease Control Rate	each 42 days up to intolerance the toxicity or PD (up to 24 months)
Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability)	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Until 21 day safety follow-up visit

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Guangxi Medical University
• Investigators: Principal Investigator: Xiaohua Hu, MD, First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: August 29, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

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; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: ALTER-L019

Drug and device information, study documents

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