Clinical trial NCT03766490: Anlotinib Hydrochloride Combined With EGFR TKIs in Advanced Non-small Cell Lung Cancer
Official title: A Prospective, Single-arm, Multicenter Study of Anlotinib Hydrochloride Combined With First-generation EGFR TKIs as Second-line Treatment in Acquired (Non-T790M Mutation) Resistance Advanced Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Small-Cell Lung
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: The First People's Hospital of Changzhou
name: Second Affiliated Hospital of Soochow University
name: Nantong University
name: Affiliated Hospital of Jiangnan University
name: Jiangyin People's Hospital
name: Changzhou No.2 People's Hospital
name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
First posted: 2018-12-06
Enrollment: 66
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
Intervention model description: Anlotinib Hydrochloride Combined With gefitinib or Icotinib
Primary purpose: TREATMENT

Brief summary: After the second-line treatment of patients with non-T790M mutations, chemotherapy with platinum-containing drugs was used, and chemotherapy-related toxicity was high. Studies have shown that bevacizumab combined with EGFR TKI have a good trend of benefit. This study is aimed to evaluate the efficacy and safety of Anlotinib Hydrochloride combined with first-generation EGFR TKIs as second-line treatment in advanced non-small cell lung cancer . The patients with IV non-small lung cancer have acquired resistance to prior first-generation EGFR TKIs and have non-T790M mutation.


Eligibility criteria: Inclusion Criteria:

* Participants must have histlogically confirmed stage IV non-small cell lung cancer .
* The initial treatment with gefitinib/icotinib evaluated PR/NC and the efficacy lasted for more than 6 months, then the disease progressed later. (The efficacy was assessed as PD according to the evaluation standard of RECIST1.1)
* At least a measurable lesion that meets the RECIST 1.1 criteria.
* Any gender. Age ≥18 years and ≤75 years
* Life expectancy \>3 months.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
* Previously, EGFR gene test showed EGFR exon 19 deletion or exon 21 (L858R) mutation, and the gene test showed no T790M mutation before enrollment.
* Adequate organ function: haemoglobin ≥ 90 g/L;neutrophils count ≥1.5×109/L; platelet count ≥ 90 × 109/L; total bilirubin ≤ 1.5 × ULN ;ALT \< 2 × ULN, (ALT \< 5 × ULN, for those with liver metastases);AST \< 2 × ULN, (AST \< 5 × ULN, for those with liver metastases); Cr≤1.5× ULN.
* Echocardiography : LVEF≥50%
* 12-leads electrocardiogram : QTcF\<450ms (man), \<470ms(woman)
* Patient informed consent and signed written consent
* Patient compliance was good and voluntary follow-up, treatment, laboratory testing, and other research steps were performed as planned.

Exclusion Criteria:

* The patient has previously received anti-tumor therapy for EGFR TKIs other than gefitinib and ectinib for lung cancer.
* Patients that cannot detect EGFR gene, or patients with known T790M mutation.
* Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer).
* CT or MRI shows that the tumor lesion is ≤ 5 mm from the large vessel, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor.
* Active brain metastasis, cancerous meningitis, spinal cord compression patients.
* Other active malignancies that require simultaneous treatment.
* Has a history of malignant tumors in the past 5 years.
* Patients with previous anti-tumor treatment-related adverse reactions who have not recovered to NCI-CTC AE≤1.
* Abnormal coagulation ,with bleeding tendency or undergoing thrombolysis or anticoagulant therapy.
* Renal insufficiency: urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g, or creatinine clearance \<60ml / min.
* Severe acute or chronic infection requiring systemic treatment.
* Suffering from severe cardiovascular disease: myocardial ischemia ,myocardial or arrhythmia.
* Clinically significant hemoptysis occurred within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or a clear tendency to hemorrhage.
* Untreated active hepatitis : Hepatitis B or Hepatitis C

Primary outcomes:
measure: PFS（Progress free survival）
timeFrame: each 42 days up to PD or death(up to 24 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Quality of Life(QoL)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated hospital of soochow university
state: Jangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Min Tao, Doctor
role: PRINCIPAL_INVESTIGATOR
References: