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) (ANSWER)

Hengrui Medicine

Status and phase: Unknown; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Apatinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02332512

HR-APTN-Ⅲ-NSCLC-02

Details and patient eligibility

About

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.

Enrollment: 417 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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417 participants in 2 patient groups, including a placebo group

Apatinib

Experimental group

Description:

Apatinib tablet administered orally, 750 mg,once daily until progression

Treatment:

Drug: Apatinib

Placebo

Placebo Comparator group

Description:

Placebo tablet administered orally, once a day until progression

Treatment:

Drug: Placebo