The efficacy and safety of EGFR TKIs combined with bevacizumab or radiotherapy in EGFR mutant NSCLC patients after assessing disease stability

• Register: ChiCTR
• Last refreshed on: 4 December 2018
• Main ID: ChiCTR1800019856
• Date of registration: 2018-12-02
• Prospective Registration: Yes
• Primary sponsor: The First Hospital Affiliate to AMU (Southwest Hospital)
• Public title: The efficacy and safety of EGFR TKIs combined with bevacizumab or radiotherapy in EGFR mutant NSCLC patients after assessing disease stability
• Scientific title: The efficacy and safety of EGFR TKIs combined with bevacizumab or radiotherapy in EGFR mutant NSCLC patients after assessing disease stability
• Date of first enrolment: 2019-01-01
• Target sample size: EGFR-TKIs group:150;Combined treatment group 1:150;Combined treatment group 2:150;Combined treatment group 3:150;
• Recruitment status: Pending
• URL: http://www.chictr.org.cn/showproj.aspx?proj=28773
• Study type: Interventional study
• Study design: Cohort study
• Phase: Post-market

Countries of recruitment

China

Contacts

• Name: Zhou Xiangdong
• Affiliation: The Frist Hospital Affiliated to AMU (Southwest Hospital)

• Name: Zhou Xiangdong
• Affiliation: The Frist Hospital Affiliated to AMU (Southwest Hospital)

Key inclusion & exclusion criteria

Inclusion criteria: 1. the informed consent form has been signed, and according to the judgment of the researcher, the patient can comply with the study plan;
2. histology and cytology (don't accept based on sputum cytology alone) confirmed not surgical treatment of locally advanced (III b period, not suitable for multidisciplinary therapy), metastatic (IV) or recurrent patients with squamous cell non-small cell lung cancer;
3. genetic testing confirmed EGFR sensitive mutations (including 19 exon deletion mutations, 21 exon L858R mutations, L8761Q mutations, G719X mutations, etc.) or 20 exon T790M mutations;
4. first-line treatment with egfr-tki was effective for patients whose duration was more than 6 months, and RECIST 1.1 was evaluated as SD twice in a row;
5. be at least 18 years old;
6. score of physical status (ECOG PS) 0-2 points in the eastern tumor cooperative group;
7. the expected survival time is more than 12 weeks;
8. measurable lesions are available at baseline. In response to solid tumor response evaluation criteria (RECIST) version 1.1, there was at least one measurable lesion;
9. enough hematology function: neutrophils absolute value (ANC) acuity 1.5 x 10^9/L, and the platelet count 80 x 10^9/L, or higher acuity 9 g/dL and hemoglobin (can maintain blood transfusion or beyond the level) enough liver function: total bilirubin < 1.5 x normal limit (ULN), and does not exist in patients with liver metastasis, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN; For patients with liver metastasis, both <5 x ULN;
10. adequate renal function: the calculated value of serum creatinine is less than or equal to 1.5x ULN or creatinine clearance rate is greater than or equal to 50mL/min, and the urine test results show that urine protein <2+. For patients with urinary protein greater than or equal to 2+ detected by urine paper at baseline, 24-hour urine collection should be conducted and the protein content in urine within 24 hours must be less than or equal to 1 g before inclusion;
11. within 7 days before the study and treatment, the international standard ratio (INR) is less than or equal to 1.5, and part of the prothrombin time (PTT or aPTT) is less than or equal to 1.5 x ULN;
12. for women who are not postmenopausal (non-therapeutic induced amenorrhea for more than 12 months) or who have not undergone sterilization (removal of ovaries and/or uterus), they agree to remain abstinent or use a single or combined contraceptive method with an annual loss of less than 1% during the treatment period and for at least 6 months after the last administration of the study drug;
13. for men: agree to remain abstinent during treatment and for at least 6 months after the last administration of the study drug or to use condoms in combination with other contraceptive methods (with an annual loss of less than 1%) and agree to avoid sperm donation during the same period.
Exclusion criteria: 1. mixed adenosquamous carcinoma dominated by squamous components in bevacizumab group was proposed;
2. evidence of central nervous system (CNS) metastasis exists in patients, except those without any symptoms or those with symptoms but with stable condition at least 28 days after CNS metastasis treatment;
3. the history of hemoptysis in the bevacizumab group was included (defined as the single event blood loss of > 2.5 ml within the first 3 months of random);
4. imaging examination found evidence of tumor invasion of main blood vessels. The investigator or local radiologist must rule out evidence that the tumor is completely adjacent, surrounds, or extends into the main vascular lumen, such as the pulmonary artery or superior vena cava;
5. major surgery (including open biopsy) or severe trauma were performed within the first 28 days randomly, or major surgery was expected during the study period;
6. tissue chip biopsy or other minor surgery shall not be accepted within 7 days before the start of the study treatment, except for vascular access device implantation. However, vascular access devices should be implanted 2 days or earlier before the start of the study;
7. aspirin (325 mg/ day) or other non-steroidal anti-inflammatory drugs known to inhibit platelet function are currently or recently used (within 10 days of the first administration of bevacizumab);
8. currently or recently (within 10 days of the first administration of bevacizumab), a full dose of oral or extrenteral anticoagulants or thrombolytic drugs is used for therapeutic purposes. Anticoagulants are permitted for preventive purposes;
9. there is a history or evidence of hereditary hemorrhagic constitution or coagulation disorder that increases the risk of bleeding;
10. hypertension cannot be controlled (blood pressure: systolic >150 mmHg and/or diastolic >100 mmHg);
11. previous history of hypertensive crisis or hypertensive encephalopathy;
12. clinically significant (active) cardiovascular disease, including but not limited to cerebrovascular accident (CVA) or transient ischemic attack (TIA) (random before 6 months or less), myocardial infarction (random before 6 months or less), unstable angina and congestive heart failure (New York heart association classification II degrees or higher) or during the study period need medication, and may interfere with the treatment regularity or serious arrhythmia is not controlled by the drug;
13. serious vascular diseases (including but not limited to aortic aneurysms requiring surgical repair or recent arterial thrombosis) were observed in the first 6 months of randomization;
14. there are unhealed wounds, active peptic ulcers or fractures;
15. a history of abdominal fistula, gastrointestinal perforation or intraperitoneal abscess was randomly observed in the first 6 months;
16. be pregnant or breast-feeding, or plan to become pregnant during the study period;
17. received any other trial medication or participated in any other clinical trial within 28 days prior to randomization;
18. known allergy to bevacizumab and Chinese hamster ovarian cell products or other recombinant human or humanized antibodies or erlotinib or any of its adjuvants and other chemotherapy drugs;
19. there is evidence of persistent or active infection requiring intravenous antibiotics; Any other disease, nervous system or metabolic disorder; Physical examination results or laboratory results reasonably suspect that there is a contraindicat

Age minimum: 18
Age maximum: 80
Gender: Both

Health Condition(s) or Problem(s) studied

Lung cancer

Intervention(s)

EGFR-TKIs group:EGFR-TKIs treatment;Combined treatment group 1:EGFR-TKIs combined with bevacizumab;Combined treatment group 2:EGFR-TKIs combined with radiotherapy;Combined treatment group 3:EGFR-TKIs combined with I125;

Primary Outcome(s)

PFS;

Source(s) of Monetary Support

Clinical medical research program of The First Hospital Affilated to AMU

Ethics review

Status: Not approved
Approval date: 26/08/2013
Contact: