Apatinib in the Treatment of Advanced Non-squamous Non-small Cell Lung Cancer

Apatinib in the Treatment of Advanced Non-squamous Non-small Cell Lung Cancer:a Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study

Apatinib is a new kind of Vascular endothelial growth factor receptor(VEGFR) tyrosine kinase inhibitors (TKIs). The investigators have finished the preclinical and phase I and phase II clinical study for apatinib and found its satisfactory anti-tumor activity and tolerated toxicities. A disease-control rate of 75% was found in lung cancer patients. In the present phase III trial, the investigators will further evaluate the efficacy and toxicities of apatinib in the treatment of advanced non-squamous non-small cell lung cancer.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: apatinib; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Cancer Center of Sun Yat-Sen University (CCSU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients 18 to 70 years of age
2. Documented pathological evidence of advanced non-squamous non-small cell lung cancer with measurable lesions
3. Failure of epidermal-growth-factor receptor (EGFR) TKIs target treatment and second-line or more regimens of chemotherapy
4. Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 1
5. Patients had to have recovered from any toxic effects of therapy
6. Patients with brain/meninges metastasis should keep stable disease for 2 months before randomisation
7. Adequate hematologic and biochemical values were required

Exclusion Criteria:

1. Presence of small-cell lung cancer alone or with NSCLC
2. Pregnant or breast-feeding women
3. Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure > 140 mmHg，diastolic pressure > 90 mmHg), cardiac ischemia and infarction, ventricular arrhythmias(QT ≥ 440ms) and grade 1 cardiac insufficiency
4. Difficulties in taking pills (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction)
5. Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy
6. ≥ CTCAE 2 pneumorrhagia or ≥ CTCAE 3 hemorrhage in other organs within 4 weeks
7. Bone fracture or wounds that was not cured for a long time
8. Arterial thrombus or phlebothrombosis within 6 months and taking anticoagulant agents
9. Mental diseases and psychotropic substances abuse
10. Previous treatment with an experimental agent within 4 weeks
11. Previous treatment with VEGFR、platelet derived growth factor receptor(PDGFR) TKIS
12. Other coexisting malignant disease (apart from basal-cell carcinoma and carcinoma in situ of uterine cervix)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; po，QD； 28 days every cycle
Experimental: Apatinib; 750 mg，po，QD； 28 days every cycle	Drug: apatinib; 750 mg，po，QD； 28 days every cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression-free survival as the time from randomization to documented disease progression according to response evaluation criteria in solid tumors (RECIST) or death.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	ORR was the percentage of patients who got partial or complete response	24 months
Overall Survival(OS)	OS was determined from date of enrollment until death or the date the patient was recorded alive of last follow-up	24 months
Toxicity	Adverse events (AEs) were recorded, graded for toxicity using the NCI-CTC, and assessed by the investigator for any relationship with treatment.	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Li Zhang, MD, Cancer Center of Sun Yat-Sen University (CCSU)

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Anticipated): March 1, 2014

Study Registration Dates

• First Submitted: January 31, 2011
• First Submitted That Met QC Criteria: January 31, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Estimate): December 9, 2013
• Last Update Submitted That Met QC Criteria: December 5, 2013
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Apatinib; Non-small Cell Lung Cancer; VEGFR TKIs
• 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; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: HENGRUI 20110301