Safety and Efficacy of Anlotinib Hydrochloride Combined With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in Treating Advanced Non-small-cell Lung Cancer (NSCLC) Patients With Acquired Resistance to EGFR TKIs
Overview
- Phase
- Not Applicable
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Progression free survival（PFS）
Overview
Brief Summary
The Single-arm, multicenter study evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in treating Advanced NSCLC With acquired Resistance to EGFR TKIs
Detailed Description
EGFR TKI have been approved as first-line treatment in NSCLC patients harboring EGFR mutation. However, the acquired resistance of EGFR-TKI occurs almost constantly. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor and primary targeted to Vascular Endothelial Growth Factor Receptor (VEGFR), fibroblast growth factor receptor (FGFR) , platelet-derived growth factor receptor (PDGFR) and c-Kit. The ALTER-0303 trial showed that patients with advanced non-small cell lung cancer (NSCLC) who received anlotinib as third-line or further therapy had more survival benefit. The Single-arm, multicenter study evaluate the safety and efficacy of Anlotinib Hydrochloride combined with EGFR TKIs in treating Advanced NSCLC With acquired Resistance to EGFR TKIs
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up;
- •Males or females aged 18 Years to 75 Years
- •The patients should be confirmed with EGFR mutation \[e.g., T 790 M , exon 19 deletion, L 858 R, etc\],
- •Cytologically or histologically confirmed locally advanced and / or metastatic non-small cell lung cancer (NSCLC).
- •Patients should be using the EGFR TKI monotherapy as the first line treatment and meet the following criteria:
- •Patients who showed objective clinical benefit from treatment with an EGFR
- •TKI as defined by either:
- •Patients who showed complete (CR) or partial response (PR) ≥ 4 months, or
- •Patients who maintained stable disease (SD) status ≥ 6 months
- •Patients who showed
Exclusion Criteria
- •Small cell lung cancer (including Small cell lung cancer mixed with non-small cell lung cancer);
- •Imaging (CT or MRI) showed that the distance between the lesion and the large vessels was less than 5 mm, or there were central tumors invading the local large vessels, or there were obvious pulmonary cavity or necrotic tumors.
- •Patients with active brain metastasis, cancerous meningitis, spinal cord compression, or with brain or pia mater diseases detected by CT or MRI at screening time (patients with stable symptoms and complete treatment 14 days before enrollment may be admitted to the group, but no symptoms of cerebral hemorrhage should be confirmed by craniocerebral MRI, CT or venography evaluation).
- •Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥ 90 mmHg, despite using the optimal medical treatment;
- •Patients are participating in other clinical studies, or there are less than four weeks before the end of the previous clinical study.
- •Other active malignant tumors requiring concurrent treatment;
- •The patient has a history of malignant tumors. Patients with basal cell carcinoma of skin, superficial bladder cancer, squamous cell carcinoma of skin or carcinoma of cervix in situ who had undergone possible curative treatment and had no disease recurrence within 5 years after the initiation of curative treatment are permitted.
- •Patients had treatment related adverse reactions after previous systemic anti-tumour therapy (except hair loss), but did not recover to NCI-CTCAE ≤ 1 grade.
- •The patient has the coagulation disorders (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or activated partial thromboplastin time (APTT) \> 1.5 ULN), or bleeding tendency, or undergoing thrombolysis or anticoagulation therapy; Note: On the premise that the International Standardized Ratio of Prothrombin Time (INR) is less than 1.5, low doses of heparin (0.6 million to 12,000 U per day for adults) or aspirin (less than 100 mg per day) are allowed for preventive purposes.
- •Renal insufficiency: Urinary routine indicated that urinary protein ≥ ++ or confirmed 24-hour urinary protein ≥ 1.0 g;
Arms & Interventions
Anlotinib Hydrochloride combined with EGFR-TKI
Patients receive anlotinib (12 mg orally daily for 14 days every 21 days cycle) combined with one of following EGFR-TKIs: Gefitinib is administered 250 mg once per day. Erlotinib is administered 150 mg once per day , or Icotinib is administered 125 mg three times per day, until disease progression or untolerated toxicity.
Intervention: Anlotinib Hydrochloride (Drug)
Outcomes
Primary Outcomes
Progression free survival（PFS）
Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year
Secondary Outcomes
- Disease Control Rate(DCR)(Up to 1 year)
- 6 months and 12 months progression-free survival (PFS) Rate(Up to 1 year)
- objective response rate (ORR)(Up to 1 year)
- Overall survival (OS)(From the date of randomization to the date of death from any cause，assessed up to 2 year)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 21 days post-the last treatment)
- progression-free survival (PFS) for different types of EGFR mutation(Up to 1 year)
- Overall survival (OS) for different types of EGFR mutation(Up to 2 year)