Clinical trial NCT03736837: Study of Anlotinib Combined With Icotinib as the First-line Treatment in Patients With EGFR Mutation-positive NSCLC
Official title: A Multi-center, One-arm Clinical Study of Anlotinib Combined With Icotinib as the First-line Treatment in Patients With EGFR Mutation-positive Advanced NSCLC. The Trial Aims to Evaluate the Efficacy and Safety of This Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: sensitive EGFR mutations
anlotinib
icotinib
first line
cancer
non-squamous NSCLC
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
Collaborators: name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
First posted: 2018-11-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy and safety of Anlotinib plus Icotinib as the first-line treatment in patients with sensitive EGFR mutations advanced non-small cell lung cancer.

Detailed description: Anlotinib Hydrochloride is a kind of innovative medicines approved by State Food and Drug Administration（CFDA:2011L00661） which was developed by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent
2. 18-75years，ECOG PS：0-2，Life expectancy of more than 3 months，with measurable lesion ( RECIST1.1)
3. Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC（according to the 8th Edition of the AJCC Staging system）with EGFR 19 del and/or 21 L858R gene mutation
4. Has not received chemotherapy or other targeted therapies；For recurrent disease, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant chemotherapy may be accepted, but recurrence occurs after ≥6 months from stopping treatment.
5. ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction；Previously received radiation therapy, but the radiotherapy area must be \<25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment;
6. Main organs function is normal
7. Patients of brain metastases with asymptomatic or mild symptoms can be enrolled
8. The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.

Exclusion Criteria:

1. Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
2. ALK-positive NSCLC
3. Central Lung tumors that Imaging (CT or MRI) shows tumor lesions invade local large blood vessels; or with significant pulmonary cavum or necrotizing
4. Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 14 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
5. The patient is participating in other clinical studies or Participated in other anti-tumor drug clinical trials within 4 weeks before enrollment
6. With other active malignancies that require simultaneous treatment
7. Has a history of malignant tumors. Except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone curative treatment and have no disease recurrence within 5 years after the start of treatment
8. Patients with adverse reactions derived from previous therapies (excluding hair loss), which is over level 1 in CTC AE (4.0)
9. abnormal blood coagulation (INR\>1.5 or PT \> ULN + 4s or APTT \> 1.5 ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy
10. renal insufficiency: urinary protein ≥ ++, or 24-hour urine protein ≥ 1.0g;
11. The effect of surgery or trauma has been eliminated for less than 14 days before enrollment
12. Severe acute or chronic infections requiring systemic treatment
13. Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias
14. Patients with peripheral neuropathy which is over level 2 in CTC AE (4.0), except for trauma
15. respiratory syndrome (dyspnea≥CTC AE 2), severe pleural effusion, ascites, pericardial effusion
16. Long-term unhealed wounds or fractures
17. Decompensated diabetes or other ailments treated with high doses of glucocorticoids
18. with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus)
19. hemoptysis (daily hemoptysis\>50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency
20. Thrombosis events occurring within 12 months prior to enrollment
21. Planned to get systemic anti-tumor therapy during this study；EF-RT was performed within 4 weeks before enrollment or limited field radiotherapy within 2 weeks before grouping
22. Hypertension (systolic blood pressure≥140 mmHg or diastolic blood pressure≥90 mmHg) that is still uncontrollable using two or more combination therapies
23. History of psychotropic substance abuse and inability to quit or have mental disorders
24. HIV test positive history or AIDS; untreated active hepatitis; combined with hepatitis B and hepatitis C co-infection

Primary outcomes:
measure: PFS（Progress free survival）
timeFrame: each 42 days up to PD or death (up to 24 months)
Secondary outcomes:
measure: OS（Overall Survival）
timeFrame: From enrollment until death (up to 24 months)
measure: ORR（Objective Response Rate）
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: DCR（Disease Control Rate）
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Adverse Events
timeFrame: Until 30 day safety follow-up visit
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei Provincial People's Hospital
state: Hebei
city: Hohhot
country: China
facility: Neimenggu Autonomous Region People's Hospital
state: Neimenggu
city: Hohhot
country: China
facility: Neimenggu Medical University Affiliated Hospital
state: Neimenggu
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Dingzhi Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.