Apatinib in the Treatment of Patients With EGFR T790M-Negative NSCLC

A Randomized, Controlled Phase II Clinical Trial of Apatinib in Combination With EGFR-TKI Versus EGFR-TKI for Non-squamous, Non-small Cell Lung Cancer(NSCLC) With T790M-negative After the Failure of EGFR-TKI Therapy

This phase 2 study is designed to evaluate the safety and activity of apatinib,a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2, in combination with EGFR-TKI in NSCLC with T790M-negative after the failure of EGFR-TKI therapy.

Study Overview

• Status: Unknown
• Conditions: Neoplasms; Respiratory Tract Diseases; Lung Diseases; Thoracic Neoplasms; Non-Small-Cell Lung
• Intervention / Treatment: Drug: Apatinib; Drug: EGFR-TKI

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rui Shi, MD; Phone Number: +8613880898008; Email: shirui729@hotmail.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
      • Contact: Panwen Tian, MD; Phone Number: +8618036675920
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital
    • Chengdu, Sichuan, China, 610071
      • Sichuan Provincial People's Hospital
      • Contact: Rui Ao, MD; Phone Number: +8618036675290; Email: aorui1040@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed stage IIIB, IV non-squamous non-small cell lung cancer, with measurable lesions (the long axis of tumor lesions ≥ 10mm with CT, the short axis of lymph node lesions ≥ 15mm with CT, the lesions not receive radiotherapy, frozen or other local treatment);
• Patients with slow progression on first-line EGFR TKI(erlotinib / icotinib / gefitinib) treatment;
• No T790M mutation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
• Life expectancy of more than 3 months;
• Adequate bone marrow function: WBC ≥ 3.0 ×10 E+9/L, neutrophil ≥ 1.5 × 10 E+9/L, platelets ≥ 80 × 10E+9/L,Hb ≥ 10.0g/dL;a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL), a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤3UNL or ≤5UNL in case of liver metastasis, a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault);
• Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug;
• the participants volunteered to join this study should sign the informed consent forms, have better compliance in the follow-up;

Exclusion Criteria:

• Squamous cell carcinoma (including adenosquamous carcinoma); Small cell lung carcinoma (including small cell carcinoma and non-small cell mixed lung carcinoma);
• Active brain metastases, cancerous meningitis, patients with spinal cord compression;
• Rapid progression of the disease or cancer invades vital organs;
• The distance between the tumor lesion and the large blood vessel is less than 5 mm, or there is a central tumor invading local macrovascular;
• obvious pulmonary cavity or tumor necrosis;
• Uncontrollable high blood pressure;
• Grade Ⅱ or above myocardial ischemia or myocardial infarction or arrhythmia control is not good,Ⅲ ~ Ⅳ grade cardiac insufficiency, or cardiac ultrasonography showed left ventricular ejection fraction (LVEF) <50% according to the NYHA standard;
• Have a history of interstitial lung disease or patients with interstitial lung disease;
• Coagulation abnormalities (INR> 1.5 or PT> ULN + 4s or APTT> 1.5 ULN) with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
• There was significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above;
• A clinically significant bleeding symptom or bleeding tendencies such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above, or vasculitis that occurred within 3 months prior to enrollment;
• Aneurysm / venous thrombotic events such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• Arterial / venous thrombotic events such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months prior to enrollment;
• Hereditary or acquired bleeding and thrombophilia, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism；
• Long-term unhealed wounds or fractures;
• Major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;
• Unable to swallow, chronic diarrhea or intestinal obstruction;
• Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months prior to enrollment;
• Urinary protein ≥ ++, 24-hour urinary protein ≥ 1.0 g;
• Active infections require antimicrobial treatment;
• ALK gene abnormalities (gene fusion or mutation occurred);
• Pregnant or lactating women, or women unwilling or unable to take effective contraception;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apatinib combine with EGFR-TKI; Every 4 weeks 1 cycle, evaluated the efficacy and safety once every 2 cycles, treat until disease progression or intolerable toxicity	Drug: Apatinib; Apatinib mesylate tablets 250 mg qd po, if the patient can tolerate the toxic side effects, adjust the dose to 500mg qd po after 1 week.; Other Names: apatinib tablets; Drug: EGFR-TKI; Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po; Other Names: Imatinib、Gefitinib or Erlotinib
Active Comparator: EGFR-TKI; Every 4 weeks 1 cycle, evaluated the efficacy and safety once every 2 cycles, treat until disease progression or intolerable toxicity	Drug: EGFR-TKI; Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po; Other Names: Imatinib、Gefitinib or Erlotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The length of time from either the date of diagnosis or the start of treatment that half of the patients in a group of patients diagnosed with the disease are still alive.	up to 36 months
Duration of response (DOR)	From first response to the date of first documented disease progression	up to 24 months
Disease Control Rate (DCR)	the proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.	24 weeks
Overall response rate (ORR)	the proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator	24 weeks
the quality of life (QoL)	Analysis of changes from baseline using the quality of life (QoL) instrument	up to 36 months

Collaborators and Investigators

• Sponsor: Sichuan Cancer Hospital and Research Institute
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2018
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): August 30, 2022

Study Registration Dates

• First Submitted: December 26, 2017
• First Submitted That Met QC Criteria: December 26, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 3, 2018
• Last Update Submitted That Met QC Criteria: December 26, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: NSCLC; apatinib; T790 negative
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Thoracic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib; Apatinib
• Other Study ID Numbers: APTN-NSCLC-201712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No