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
Trial Snapshot
- Phase
- Phase 3
- Enrollment
- 369
- Locations
- 59
- Primary Endpoint
- Progression free survival (PFS)
Study 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident including transient ischemic attack, deep vein thrombosis and pulmonary embolism.
- •Has psychotropic substances abuse or a mental disorder.
- •Have a history of immunodeficiency.
- •Has received allogeneic organ transplantation, hematopoietic stem cell transplantation or bone marrow transplantation.
- •Has other malignancy. 17.Has participated in other anticancer drug clinical trials within 4 weeks. 18.According to the judgement of the researchers, there are other factors that may lead to the termination of the study.
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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)