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

Phase 2

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: apatinib single agent

• Registration Number: NCT02515435
• Lead Sponsor: Tongji University

Brief Summary

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.

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 Timeline

• Study Start: 2015-01-01
• Study First Submitted: 2015-07-30
• Study First Submitted QC: 2015-07-31
• Study First Posted: 2015-08-04
• Primary Completion: 2016-08-01
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-15
• Last Update Posted: 2017-08-18
• Study Completion: 2017-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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

8. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
apatinib single agent	apatinib single agent	apatinib, single agent, 500mg or 750mg Qd po, continue until disease progression

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression free survival	12 months	PFS is evaluated in 24 months since the treatment began

Trial Locations

Locations (1)

Department of Oncology, Shanghai pulmonary hospital; 🇨🇳 Shanghai, China