Clinical trial NCT03416231: Apatinib Plus Docetaxel in Advanced Non-squamous Non-small Cell Lung Cancer(NSCLC)
Official title: A Study of Combined Treatment of Apatinib With Docetaxel as Post Second-line Therapy in Advanced Non-squamous Non-small Cell Lung Cancer(NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NSCLC
Keywords: apatinib
Docetaxel
Lead sponsor: Afﬁliated Hospital of North Sichuan Medical College
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2018-01-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the effectiveness and safety of apatinib combined with docetaxel in NSCLC.


Eligibility criteria: Inclusion Criteria:

* 1. Male or female patients, age: ≥ 18 years of age;
* 2. Pathologically diagnosed late (stage IIIB, stage IV, see Annex 1) non-squamous non-small cell lung cancer with measurable lesions (CT scan of tumor lesion longer than 10 mm in diameter, shorter than 15 CT scan of lymph nodes mm, the scanning layer thickness is not more than 5 mm;
* 3. Previous drug treatment consisted of a platinum-based chemotherapy regimen (\> 1 chemotherapy regimen) for relapse or failure of treatment.
* 4. The main organs function properly, that is, within 14 days prior to the relevant indicators meet the following requirements:(1) a. Hemoglobin (HB) ≥90 g / L; (no blood transfusion within 14 days):b. neutrophil count (ANC) ≥ 1.5 × 109 / L; c. Platelet count (PLT) ≥80 × 109 / L;(2) biochemical tests to meet the following criteria:a. Total bilirubin (TBIL) \<1.5?ULN (upper limit of normal);b. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

  5. Sign the inform consent form with good compliance.

Exclusion Criteria:

* 1. Squamous cell carcinoma (including adenosquamous carcinoma); Small cell lung carcinoma (including small cell carcinoma and non-small cell mixed lung carcinoma)
* 2. Patients who had previously received docetaxel treatment were excluded
* 3. Patients with active brain metastasis, carcinomatous meningitis, or spinal compression, or disease of brain or pia mater according to the screening test, imaging, CT or MRI tests (patients who have completed the treatment and in a stable condition 21 days before screening could be included, but brain MRI, CT or venography is required to confirm that there are no brain hemorrhage symptoms).
* 4. Patients with uncontrollable hypertension (systolic blood pressure\> 140 mmHg, diastolic blood pressure\> 90 mmHg, despite optimal drug therapy).
* 5. Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms).
* 6. According to NYHA standard, grade Ⅲ \~ Ⅳ heart failure, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) \<50%.
* 7. Coagulation dysfunction (INR\> 1.5, PT\> ULN +4s or APTT\> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment.
* 8. Patients treated with anticoagulation agents or Vitamin K antagonist such as Warfarin, heparin, or other similar drugs.
* 9. Patients who had obvious hemoptysis within 2 months before screening, or experienced daily hemoptysis with a volume more than half a tea spoon (2.5ml) or above.
* 10. Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc.
* 11. Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.
* 12. Known genetic or acquired bleeding or bleeding tendency (such as hemophilia, blood coagulation dysfunction, thrombocytopenia, and hypersplenism, etc.).
* 13. Patients who have unhealed wounds or fractures for a long time.
* 14. Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening.
* 15. Patients with obvious factors affecting absorption of oral drugs, such as difficulties in swallowing, chronic diarrhea and intestinal obstruction, etc.
* 16. Occurrence of abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess within 6 months before screening.
* 17. Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.
* 18. Patients with active hepatitis B virus or hepatitis c virus infection.
* 19. Active infection requiring antimicrobial treatment, such as antibacterial, antifungal, or antiviral therapy.
* 20. Patients with clinical symptoms, or dropsy of serous cavity requiring surgical treatment (including hydrothorax, ascites, and hydropericardium).
* 21. Patients who have a history of psychotropic drug abuse and are unable to break the habit, or who have a psychogeny.
* 22. Patients who have taken part in other drug clinical tests within 4 weeks before screening.
* 23. Prior VEGFR inhibitor treatment.
* 24. Patients who formerly suffered from or currently are complicated with other uncured malignant tumors, except basal cell carcinoma, carcinoma in situ of cervix and superficial bladder cancer that have been cured.
* 25. Patients who received the treatment with potent CYP3A4 inhibitors within 7 days before screening, or potent CYP3A4 inducers within 12 days before being included.
* 26. Pregnant or lactating women, fertile patients who are unwilling or unable to take effective contraceptive measures.
* 27. Conditions determined by investigators to possibly affect the clinical study or determination of the study results.

Primary outcomes:
measure: objective response rate (ORR)
timeFrame: 6 month
Secondary outcomes:
measure: progression free survival (PFS)
timeFrame: 12 month
measure: disease control rate (DCR)
timeFrame: 6 month
measure: 6-month overall survival rate
timeFrame: 6 month
Other outcomes:
Locations:
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
Study officials:
affiliation: Afﬁliated Hospital of North Sichuan Medical College
name: Daiyuan Ma, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanchong Central Hospital
name: xin hu, M.D.
role: STUDY_DIRECTOR
affiliation: Dazhou Central Hospital
name: xiangdong fang, M.d.
role: STUDY_DIRECTOR
References:
citation: Jiang Q, Zhang NL, Ma DY, Tan BX, Hu X, Fang XD. Efficacy and safety of apatinib plus docetaxel as the second or above line treatment in advanced nonsquamous NSCLC: A multi center prospective study. Medicine (Baltimore). 2019 Jun;98(26):e16065. doi: 10.1097/MD.0000000000016065.