Clinical trial NCT02332512: Study of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)
Official title: A Randomized, Double-blind, Placebo-controlled, Phase III Trial of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Non-squamous non-small cell lung cancer
Wild-type EGFR
3rd/4th line treatment
apatinib
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-01-06
Enrollment: 417
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI). The investigators have finished the preclinical,phase I and phase II clinical studies and found its promising anti-tumor activity and tolerable toxicities. A disease-control rate of 61.1% and a mPFS of 4.7 months were showed in apatinib phase II study in patients with NSCLC.

The study aims to compare the efficacy and safety of apatinib to placebo in advanced non-squamous non-small cell lung cancer patients.


Eligibility criteria: Inclusion Criteria:

1. Subjects \>/= 18 years and \</=70 years of age at the time of Informed Consent.
2. Advanced relapsed or refractory predominantly NSCLC with documented wild-type EGFR.
3. At least one measurable lesion according to RECIST 1.1.
4. Failure of second line of chemotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. Patients must have recovered from any AEs of prior treatments before randamization.
7. Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥80×10E+9/L; ALT and AST \< 2.5×ULN; TBIL ≤1.25×ULN; Cr ≤1.25×ULN;CL\>45 ml/min.
8. Life expectancy of at least three months.
9. Written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion Criteria:

1. Presence of types of small-cell, squamous-cell, adeno-squamous-cell lung cancer.
2. Pregnant or breast-feeding women.
3. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure \>/= 140 mm Hg and/or diastolic pressure \>/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF\<50%.
4. Factors to affect oral administration(inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
5. Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy\>/= CTCAE 2 pneumorrhagia or \>/= CTCAE 3 hemorrhage in other organs within 4 weeks.
6. Bone fracture or wounds that was not cured.
7. Arterial thrombus or phlebothrombosis within 12 months and taking anticoagulant agents.
8. Mental diseases and psychotropic substances abuse.
9. Previous treatment with an trial agent within 4 weeks
10. Previous treatment with VEGFR,platelet derived growth factor receptor(PDGFR) TKIs.
11. Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
12. Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).

Primary outcomes:
measure: Overall Survival（OS)
timeFrame: 24 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 24 months
measure: Objective response rate (ORR)
timeFrame: 24 months
measure: Duration of response (DoR)
timeFrame: 24 months
measure: Disease control rate (DCR)
timeFrame: 24 months
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)
timeFrame: 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Medical Oncology, Cancer Center, Sun Yet-sen University
state: Guangdong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: