EGFR-TKIs plus anti-angiogenesis therapy in non–small cell lung cancer with EGFR mutations

• Register: ChiCTR
• Last refreshed on: 4 December 2018
• Main ID: ChiCTR1800019835
• Date of registration: 2018-12-02
• Prospective Registration: Yes
• Primary sponsor: Shanghai Pulmonary Hospital
• Public title: EGFR-TKIs plus anti-angiogenesis therapy in non–small cell lung cancer with EGFR mutations
• Scientific title: EGFR-TKIs plus anti-angiogenesis therapy in non–small cell lung cancer with EGFR mutations
• Date of first enrolment: 2019-01-01
• Target sample size: Case series:42;
• Recruitment status: Pending
• URL: http://www.chictr.org.cn/showproj.aspx?proj=33417
• Study type: Observational study
• Study design: Case series
• Phase: Post-market

Countries of recruitment

China

Contacts

• Name: Shengxiang Ren
• Affiliation: Shanghai Pulmonary Hospital

• Name: Shengxiang Ren
• Affiliation: Shanghai Pulmonary Hospital

Key inclusion & exclusion criteria

Inclusion criteria: 1. Subject's written informed consent has been obtained prior to any process, sampling, or analysis related to the study;
2. Male or female is not limited, and the age is not less than 18 years old (on the day of signing the informed consent form);
3. The patient was diagnosed as NSCLC by histology or cytology;
4. The tumor is locally advanced or metastatic NSCLC and is not suitable for radical surgery or radiotherapy;
5. There has been no systematic anti-tumor treatment in the past; the treatment used in the neoadjuvant treatment phase is not included in the treatment plan; postoperative adjuvant chemotherapy, from the end of treatment to recurrence > 6 months, does not count the number of previous chemotherapy regimens;
6. There are well-documented confirmed EGFR mutations associated with EGFR-TKI sensitivity at any time after the initial diagnosis;
7. At least one baseline tumor lesion in the patient can meet the following requirements: no previous radiotherapy, no biopsy during the screening period, and accurate or repeated measurement with CT or MRI. The longest diameter in the baseline period is =10mm (if Lymph nodes require a short axis = 15 mm). If there is only one measurable lesion, the baseline assessment is allowed to be completed at least 14 days after the screening biopsy;
8. Can swallow pills normally;
9. ECOG PS score 0~1 points, expected survival period =12 weeks;
10. Organ function meets the following criteria:
(1) Adequate bone marrow reserve (not treated with hematology or cytokine correction within 14 days prior to the first study):
(2) Absolute neutrophil count =1.5×10^9/L, platelet count =90×10^9/L, and hemoglobin =9 g/dL;
(3) Liver: serum albumin = 3.0 g / dL; total bilirubin = 1.5 times upper limit of normal (ULN), ALT and AST = 3 times ULN;
(4) Kidney: serum creatinine <1.25 times ULN;
(5) Heart: left ventricular ejection fraction (LVEF) = 50%; electrocardiogram is basically normal, average QTc <470 ms in 3 electrocardiogram during screening period;
11. Female subjects and partners who are women of childbearing age should be sterilized or must agree to use high-efficiency methods during the study period and within 1 month after the end of the study period; non-surgical sterilization Female subjects of childbearing age must have a negative serum HCG test within 3 days prior to study enrollment and must be non-lactating subjects.
Exclusion criteria: 1. Subjects have clinically symptomatic central nervous system metastases (eg, cerebral edema, need for hormonal intervention, or progression of brain metastases);
2. Asymptomatic, stable condition, no need to use steroid medication before the start of study treatment or 4 weeks of treatment; Previous systemic, radical brain or meningeal metastasis (radiotherapy or surgery), such as imaging confirmed that stability has been maintained for at least 1 month, and systemic hormone therapy has been discontinued (dose > 10 mg / day prednisone or other etc. Patients with more than 2 weeks of curative effect hormones without clinical symptoms can be included;
3. Ascites, pleural effusion or pericardial effusion with clinical symptoms require therapeutic puncture or drainage, or chest and ascites drainage within 14 days before the first dose;
4. The patient has had other malignant tumors within 5 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ; except for 3 years without radical recurrence after radical mastectomy);
5. Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg);
6. There are clinical symptoms or diseases of the heart that are not well controlled, such as: (1) heart failure above NYHA class 2 (2) unstable angina (3) myocardial infarction within 1 year (4) clinically significant on-ventricular Sexual or ventricular arrhythmia requires treatment or intervention;
7. Coagulation dysfunction (INR>2.0, PT>16s), bleeding tendency or receiving thrombolysis or anticoagulant therapy, allowing prophylactic use of low-dose aspirin, low molecular weight heparin;
8. Have a history of hemorrhage, cough/hemoptysis >2.5ml within 4 weeks before screening, or any severe grading of 3 degrees or more in CTCAE5.0, or a potential bleeding tendency, such as gastroscopy with hemorrhagic Stomach ulcer
9. Imaging shows that the tumor has invaded important blood vessels or that the patient's tumor has a high probability of invading important blood vessels during treatment and causing fatal bleeding;
10. Events of arterial/venous thrombosis occurring within 6 months prior to randomization, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
11. Known hereditary or acquired bleeding and thrombophilia (eg hemophilia patients, coagulopathy, thrombocytopenia, etc.);
12. Urine routine indicates that urine protein = ++ and confirmed that the 24-hour urine protein amount is > 1.0 g;
13. Any serious or uncontrolled eye lesions may increase the patient's safety risk as judged by the investigator;
14. A history or evidence of interstitial lung disease or the presence of non-infectious pneumonia treated with corticosteroids; or patients who may interfere with the detection or management of suspected drug-related lung toxicity;
15. Patients with congenital or acquired immunodeficiency (such as HIV-infected persons);
16. HBV DNA>500 IU/ml, HCV RNA>103 copies/ml;
17. CYP3A4 strong inhibitor was used within 1 week before the first dose, CYP3A4 strong inducer was used within 2 weeks, or CYP3A4 strong inhibitor or inducer could not be stopped during the test;
18. Patients have previously received third-generation EGFR-TKI therapy targeting EGFR-T790M mutations (including but not limited to, oct

Age minimum: 18
Age maximum: -
Gender: Both

Health Condition(s) or Problem(s) studied

Lung Cancer

Intervention(s)

Case series:EGFR-TKI+VEGFR2-TKI;

Primary Outcome(s)

Objective response rate;

Secondary Outcome(s)

12-month progression-free survival rate;Progression-free survival;Disease control rate;Adverse event;

Source(s) of Monetary Support

Shanghai Pulmonary Hospital Clinical Research Project

Ethics review

Status: Approved
Approval date: 30/11/2018
Contact:

Lei Zhang