Clinical trial NCT02733107: The Efficacy and Safety of Apatinib Combined With Etoposide in Heavily Pretreated Advanced Non-small Cell Lung Cancer
Official title: The Efficacy and Safety of Apatinib Combined With Etoposide in Advanced Non-small Cell Lung Cancer Patients Failed to Previous at Least 2rd Line Treatments
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer
Apatinib
Etoposide
Lead sponsor: Third Military Medical University
Sponsor class: OTHER
First posted: 2016-04-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
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 is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2). Etoposide is an oral preparation for lung cancer which is recommended by NCCN guideline. The investigators wondered whether these two drugs have synergistic effects when treating advanced non-small cell lung cancer patients who failed to previous at least 2nd line treatments. Thus, the aim of this trial is to investigate the efficacy and safety of apatinib combined with etoposide in heavily pretreated advanced non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

* Obtain of informed consent.
* Histologically or cytologically confirmed non-small cell lung cancer.
* World Health Organization (WHO) performance status (PS) of 0 to 2.
* Measurable lesions as defined by RECIST criteria.
* Second-line or more treatments.
* Wild type of epidermal-growth-factor receptor (EGFR).
* Life expectancy ≥12 weeks.
* 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.
* 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:

* Small cell lung cancer.
* Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
* Uncontrolled hypertension.
* Myocardial ischemia or infarction more than stage II, cardiac insufficiency.
* Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy.
* Difficulties in taking pills (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
* Hemoptysis, more than 2.5ml daily.
* Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
* Unhealed bone fracture or wound for long time.
* Received big surgery, had bone fracture or ulcer in 4 weeks.
* Urine protein≥++, or urine protein in 24 hours≥1.0g.
* Pregnant or lactating woman.

Primary outcomes:
measure: Progression free survival
timeFrame: evaluated in 24 months since the treatment began
Secondary outcomes:
measure: Objective Response Rate
timeFrame: tumor assessment every 6-8 weeks since the treatment began，up to 24 months
measure: Overall survival
timeFrame: the first day of treatment to death or last survival confirm date,up to 24 months
measure: Side effects
timeFrame: evaluated in the 24th month since the treatment began according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Daping Hospital, Third Military Medical University
state: Chongqing
Study officials:
References:
citation: Zhou C, Wu YL, Chen G, Liu X, Zhu Y, Lu S, Feng J, He J, Han B, Wang J, Jiang G, Hu C, Zhang H, Cheng G, Song X, Lu Y, Pan H, Zheng W, Yin AY. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Jul 1;33(19):2197-204. doi: 10.1200/JCO.2014.59.4424. Epub 2015 May 26.
citation: Okamoto I, Miyazaki M, Takeda M, Terashima M, Azuma K, Hayashi H, Kaneda H, Kurata T, Tsurutani J, Seto T, Hirai F, Konishi K, Sarashina A, Yagi N, Kaiser R, Nakagawa K. Tolerability of nintedanib (BIBF 1120) in combination with docetaxel: a phase 1 study in Japanese patients with previously treated non-small-cell lung cancer. J Thorac Oncol. 2015 Feb;10(2):346-52. doi: 10.1097/JTO.0000000000000395.