A Randomized, Double-blind, Multicenter Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy Versus Placebo Combined With Chemotherapy as First-line Treatment in Subjects With Advanced Non-squamous Cell Non-small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- Anlotinib hydrochloride capsule
- Conditions
- Advanced Non-squamous Cell Non-small Cell Lung Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 369
- Locations
- 59
- Primary Endpoint
- Progression free survival (PFS)
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a randomized, double-blind, multicenter phase III clinical study to evaluate efficacy and safety of anlotinib hydrochloride capsule combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in subjects with advanced non-squamous cell non-small cell lung cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Local advanced (stage IIIB / ⅢC), metastatic or recurrent (stage IV) non-squamous cell non-small cell lung cancer, has at least one measurable lesion.
- •EGFR, ALK, and ROS1 test results are negative.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, life expectancy≥ 12 weeks.
- •Has not received systemic anti-tumor treatment for advanced disease. 5.Adequate organ system function.
- •Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ; No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
- •Understood and signed an informed consent form.
Exclusion Criteria
- •1.Other histopathological types of non-small cell lung cancer. 2.Has received VEGF pathway targeted therapy including anlotinib and bevacizumab.
- •Has multiple factors affecting oral medication.
- •Has symptomatic brain metastases.
- •Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
- •Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade
- •Has any severe and / or uncontrolled diseases.
- •Has any bleeding symptoms or treated with anticoagulants or vitamin K antagonists.
- •9.Has received surgery, or unhealed wounds within 4 weeks before the first administration.
- •Has hemoptysis within 28 days before randomization.
- •Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear.
Arms & Interventions
Anlotinib hydrochloride capsule + chemotherapy
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Anlotinib hydrochloride capsule
Anlotinib hydrochloride capsule + chemotherapy
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Carboplatin injection
Anlotinib hydrochloride capsule + chemotherapy
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Pemetrexed disodium f Injection
Placebo + chemotherapy
Placebo given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Carboplatin injection
Placebo + chemotherapy
Placebo given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Pemetrexed disodium f Injection
Placebo + chemotherapy
Placebo given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) + Carboplatin injection (AUC 5mg/mL/min, intravenous drip, on Day 1) + Pemetrexed disodium f Injection (500mg / m2, intravenous drip, on Day 1).
Intervention: Placebo
Outcomes
Primary Outcomes
Progression free survival (PFS)
Time Frame: up to 48 weeks
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
Secondary Outcomes
- Disease control rate（DCR）(up to 48 weeks)
- Overall survival (OS)(up to 48 weeks)
- Disease of Response (DOR)(up to 48 weeks)
- Overall response rate (ORR) assessed by Independent Review Committee (IRC)(up to 48 weeks)