The Efficacy and Safety of Apatinib in Heavily Pretreated Advanced Non-squamous Non-small Cell Lung Cancer

Single Arm Phase II Clinical Trial to Investigate the Efficacy and Safety of Apatinib as a Single Agent in Advanced NSCLC Who Failed to at Least Two Lines Systemic Treatment, or Were Not Amendable to Receive the Second-line Standard Therapy

The development of anti-angiogenesis drugs has led to renewed enthusiasm in lung cancer treatments. Apatinib, also known as YN968D1, is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2) and also represents mild inhibition to PDGFR, c-Kit and c-src tyrosine kinases. It is an orally bioavailable, small molecule agent which is thought to inhibit VEGF-mediated endothelial cell migration and proliferation thus blocking blood vessel formation in tumor tissues. Previous studies have identified that apatinib was well tolerated at doses below 750mg daily. In phase I/II study, investigators reported an objective response rate of 68%. In a phase III trial conducted in advanced pretreated gastric cancer, the median overall survival was significantly prolonged in the apatinib group compared with placebo group. Thus, in this trial, the investigators aim to investigate the efficacy and safety of apatinib in previously treated advanced non-squamous non-small cell lung cancer.

Study Overview

• Status: Unknown
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: apatinib single agent

Detailed Description

Observing the efficacy and safety of apatinib in heavily treated non-squamous non-small cell lung cancer.

Primary Outcome Measure: Objective Response Rate Secondary Outcome Measures: Progression free survival, overall survival, Side effects, Quality Of Life

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Department of Oncology, Shanghai pulmonary hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Obtain of informed consent.
2. Aged 18 years and over.
3. Histologically or cytologically confirmed non-squamous non-small cell lung cancer.
4. World Health Organization (WHO) performance status (PS) of 0 to 2.
5. Measurable lesions as defined by RECIST criteria.
6. Life expectancy ≥12 weeks.
7. Progressed after at least two lines systemic treatment, or were not amendable to receive the current standard therapy

7. Organ functions normal, as defined below, within two weeks of randomization: Hb≥90g/L Absolute neutrophils count(ANC)≥1.5×109/L Platelets≥80×109/L Serum bilirubin≤2×ULN; Aspartate transaminase(AST) and alanine transaminase (ALT)≤2.5×ULN(≤5×ULN if liver metastases) Creatinine clearance≥45ml/min or Cr≤1.25×ULN 8. Females of child-bearing potential must have negative serum pregnancy test. Sexually active males and females (of childbearing potential) willing to practice contraception during the study.

Exclusion Criteria:

1. Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer.
2. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
3. Tumor invade big vessels or close to big vessels (less than 5mm)
4. Obvious cavity or necrosis formed in the tumor
5. Uncontrolled hypertension
6. Myocardial ischemia or infarction more than stage II, cardiac insufficiency.
7. Abnormal coagulation (INR>1.5 or PT>ULN+4, or APTT>1.5 ULN), bleeding tendency or receiving coagulation therapy
8. Hemoptysis, more than 2.5ml daily
9. Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
10. Unhealed bone fracture or wound for long time
11. Received big surgery, had bone fracture or ulcer in 4 weeks.
12. Urine protein≥++, or urine protein in 24 hours≥1.0g
13. Pregnant or lactating woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apatinib single agent; apatinib, single agent, 500mg or 750mg Qd po, continue until disease progression	Drug: apatinib single agent; For those heavily treated non-squamous non-small cell lung cancer, treat with apatinib single agent, 500mg or 750mg Qd, p.o based on the status of patient, continue until disease progression, dose reduction was admitted; Other Names: YN968D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	To evaluate Objective response rate every 6-8 weeks after the initiation of apatinib.	tumor assessment every 2 cycles after the initiation of apatinib，up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	PFS is evaluated in 24 months since the treatment began	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	evaluated in the 24th month since the treatment began	12 months
side effects	evaluated in the 24th month since the treatment began according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	12 months
Quality of life	evaluated in the 24th month since the treatment began	12 months

Collaborators and Investigators

• Sponsor: Tongji University

Publications and helpful links

General Publications

• Wu F, Zhang S, Xiong A, Gao G, Li W, Cai W, Su C, Chen X, Zhou F, Zhao J, Ren S, Zhou C. A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non-small-cell Lung Cancer. Clin Lung Cancer. 2018 Nov;19(6):e831-e842. doi: 10.1016/j.cllc.2018.06.002. Epub 2018 Jun 27.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: July 31, 2015
• First Posted (Estimate): August 4, 2015

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: safety; NSCLC; apatinib; efficacy
• 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: FK1405