Anlotinib Hydrochloride Combined With EGFR TKIs in Advanced Non-small Cell Lung Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Anlotinib Hydrochloride plus gefitinib or icotinib
|
Drug: Anlotinib Hydrochloride
Capsule, P.O. 12mg qd ,days 1-14, 21 days a cycle
Drug: Gefitinib
Tablet, P.O. 250mg qd
Drug: Icotinib
Tablet, P.O. 125mg tid
|
Outcome Measures
Primary Outcome Measures
- PFS（Progress free survival） [each 42 days up to PD or death(up to 24 months)]
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Secondary Outcome Measures
- Overall Survival (OS) [From randomization until death (up to 24 months)]
OS is defined as the time until death due to any cause.
- Objective Response Rate (ORR) [each 42 days up to intolerance the toxicity or PD (up to 24 months)]
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
- Quality of Life(QoL) [each 42 days up to intolerance the toxicity or PD (up to 24 months)]
use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
- Disease Control Rate (DCR) [each 42 days up to intolerance the toxicity or PD (up to 24 months)]
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants must have histlogically confirmed stage IV non-small cell lung cancer .
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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)
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At least a measurable lesion that meets the RECIST 1.1 criteria.
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Any gender. Age ≥18 years and ≤75 years
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Life expectancy >3 months.
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Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
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Previously, EGFR gene test showed EGFR exon 19 deletion or exon 21 (L858R) mutation, and the gene test showed no T790M mutation before enrollment.
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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.
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Echocardiography : LVEF≥50%
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12-leads electrocardiogram : QTcF<450ms (man), <470ms(woman)
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Patient informed consent and signed written consent
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Patient compliance was good and voluntary follow-up, treatment, laboratory testing, and other research steps were performed as planned.
Exclusion Criteria:
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The patient has previously received anti-tumor therapy for EGFR TKIs other than gefitinib and ectinib for lung cancer.
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Patients that cannot detect EGFR gene, or patients with known T790M mutation.
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Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer).
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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.
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Active brain metastasis, cancerous meningitis, spinal cord compression patients.
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Other active malignancies that require simultaneous treatment.
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Has a history of malignant tumors in the past 5 years.
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Patients with previous anti-tumor treatment-related adverse reactions who have not recovered to NCI-CTC AE≤1.
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Abnormal coagulation ,with bleeding tendency or undergoing thrombolysis or anticoagulant therapy.
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Renal insufficiency: urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g, or creatinine clearance <60ml / min.
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Severe acute or chronic infection requiring systemic treatment.
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Suffering from severe cardiovascular disease: myocardial ischemia ,myocardial or arrhythmia.
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Clinically significant hemoptysis occurred within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or a clear tendency to hemorrhage.
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Untreated active hepatitis : Hepatitis B or Hepatitis C
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated hospital of soochow university | Suzhou | Jangsu | China |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- The First People's Hospital of Changzhou
- Second Affiliated Hospital of Soochow University
- Nantong University
- Affiliated Hospital of Jiangnan University
- Jiangyin People's Hospital
- Changzhou No.2 People's Hospital
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
- Principal Investigator: Min Tao, Doctor, The First Affiliated Hospital of Soochow University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALTER-L010