Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Apatinib

Tyrosine Kinase Inhibitors

Gefitinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

(Part A) Phase I, Open-label, Dose-escalation Study Escalating doses(500mg, 750mg, or 250mg) of Apatinib in combination with 250mg Gefitinib daily orally. Participants may continue to receive treatment until progress or intolerable.

(Part B)Multicenter, Randomized, Double-Blind Study Apatinib (dose determined from Part A of study) in combination with 250mg Gefitinib.

(Part A) Not Applicable

(Part B) Placebo in combination with 250mg Gefitinib. Participants may continue to receive treatment until progress or intolerable.

Patients will be treated with Apatinib, 250/500/750 mg(dose determined from Part A of study) p.o., daily

Patients will be treated with Gefitinib, 250 mg p.o., daily

Placebo

Hongyun Zhao

Hongyun Zhao, PhD

The main purpose of this study is to evaluate the safety and efficacy of Apatinib in combination with Gefitinib as compared to placebo in combination with Gefitinib in participants with stage ⅢB-IV Non-squamous non-small-cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of Apatinib in combination with Gefitinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).

A Study of Gefitinib With or Without Apatinib in Patients With Advanced Non-squamous Non-Small-Cell Lung Cancer Harboring EGFR Mutations

A Multicenter, Randomized,Double-Blind Study of Gefitinib in Combination With Apatinib or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Advanced Non-squamous Non-Small-Cell Lung Cancer

Determine the safety, tolerability and DLTs of Apatinib in Combination With Gefitinib

MTD was determined by testing increasing doses up to 750 mg daily (qd) on dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria (CTC) Grade 4 Neutropenia in specific conditions, platelets \< 25,000 cells/mL; specific non-hematologic/biochemical toxicities CTC Grade 3 or 4; additionally, any toxicity considered by the investigator severe enough was designated a DLT); CTC Version 2 were used.

Time from the date of enrolment until documented progression or death, whichever occurs first.

Time from the date of enrolment until death from any cause.

Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment

Achievement of objective response or stable disease for at least 6 weeks

Interval from the date of first documentation of objective response by RECIST to the date of first documented progression or relapse

including adverse events, physical examination, vital signs (including Blood Pressure(BP)), clinical chemistry and hematology

Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration

Area under the plasma concentration time profile after single dose from time zero to the next dose

Predose concentration during multiple dosing

Metabolite to parent ratio for Area Under roc Curve (tau)

Spots Global Cancer Trial Database for egfr tyrosine kinase inhibitors plus vegfr inhibitors