Clinical trial NCT02515435: The Efficacy and Safety of Apatinib in Heavily Pretreated Advanced Non-squamous Non-small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: apatinib
NSCLC
safety
efficacy
Lead sponsor: Tongji University
Sponsor class: OTHER
First posted: 2015-08-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: tumor assessment every 2 cycles after the initiation of apatinib，up to 24 months
Secondary outcomes:
measure: Progression free survival
timeFrame: 12 months
Other outcomes:
measure: Overall survival
timeFrame: 12 months
measure: side effects
timeFrame: 12 months
measure: Quality of life
timeFrame: 12 months
Locations:
city: Shanghai
country: China
facility: Department of Oncology, Shanghai pulmonary hospital
Study officials:
affiliation: Shanghai Pulmonary Hospital, Tongji University
name: caicun zhou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.