ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03389256
Recruitment Status : Not yet recruiting
First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Sponsor:
Collaborator:
Jiangsu HengRui Medicine Co., Ltd.
Information provided by (Responsible Party):
Juan LI, MD, Sichuan Cancer Hospital and Research Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lung Diseases Neoplasms Respiratory Tract Diseases Thoracic Neoplasms Non-Small-Cell Lung Drug: Apatinib Drug: EGFR-TKI Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : December 30, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : August 30, 2022

Resource links provided by the National Library of Medicine


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 Name: apatinib tablets

Drug: EGFR-TKI
Imatinib tablets, 125 mg tid po; gefitinib tablets, 250 mg qd po; erlotinib tablets, 150 mg qd po
Other Name: 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 Name: Imatinib、Gefitinib or Erlotinib




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: up to 24 months ]
    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


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: up to 36 months ]
    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.

  2. Duration of response (DOR) [ Time Frame: up to 24 months ]
    From first response to the date of first documented disease progression

  3. Disease Control Rate (DCR) [ Time Frame: 24 weeks ]
    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.

  4. Overall response rate (ORR) [ Time Frame: 24 weeks ]
    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

  5. the quality of life (QoL) [ Time Frame: up to 36 months ]
    Analysis of changes from baseline using the quality of life (QoL) instrument



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03389256


Contacts
Contact: Juan Li, MD +8613880276636 dr.lijuan@gmail.com
Contact: Rui Shi, MD +8613880898008 shirui729@hotmail.com

Locations
China, Sichuan
Sichuan Cancer Hospital
Chengdu, Sichuan, China, 610041
West China Hospital, Sichuan University Not yet recruiting
Chengdu, Sichuan, China, 610041
Contact: Panwen Tian, MD    +8618036675920      
Sichuan Provincial People's Hospital Not yet recruiting
Chengdu, Sichuan, China, 610071
Contact: Rui Ao, MD    +8618036675290    aorui1040@hotmail.com   
Sponsors and Collaborators
Sichuan Cancer Hospital and Research Institute
Jiangsu HengRui Medicine Co., Ltd.

Responsible Party: Juan LI, MD, MD, Sichuan Cancer Hospital and Research Institute
ClinicalTrials.gov Identifier: NCT03389256     History of Changes
Other Study ID Numbers: APTN-NSCLC-201712
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juan LI, MD, Sichuan Cancer Hospital and Research Institute:
apatinib
T790 negative
NSCLC

Additional relevant MeSH terms:
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Thoracic Neoplasms
Neoplasms by Site
Gefitinib
Erlotinib Hydrochloride
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action