A Efficacy and Safety 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

Phase 3

• Conditions: Advanced Non-squamous Cell Non-small Cell Lung Cancer
• Interventions: Drug: Carboplatin injection; Drug: Anlotinib hydrochloride capsule; Drug: Pemetrexed disodium f Injection; Drug: Placebo

• Registration Number: NCT04439890
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-08-08
• Status Verified: 2020-06
• Study First Submitted: 2020-06-18
• Study First Submitted QC: 2020-06-18
• Last Update Submitted: 2020-06-18
• Study First Posted: 2020-06-19
• Last Update Posted: 2020-06-19
• Primary Completion: 2021-06-01
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 369

Inclusion Criteria

• 1. Local advanced (stage IIIB / ⅢC), metastatic or recurrent (stage IV) non-squamous cell non-small cell lung cancer, has at least one measurable lesion.

  2. EGFR, ALK, and ROS1 test results are negative. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, life expectancy≥ 12 weeks.

  3. Has not received systemic anti-tumor treatment for advanced disease. 5.Adequate organ system function. 6. 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.

  4. 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.

  3. Has multiple factors affecting oral medication. 4. Has symptomatic brain metastases. 5. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.

  4. Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.

  5. Has any severe and / or uncontrolled diseases. 8. 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.

  10. Has hemoptysis within 28 days before randomization. 11. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear.

  11. Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident including transient ischemic attack, deep vein thrombosis and pulmonary embolism.

  12. Has psychotropic substances abuse or a mental disorder. 14. Have a history of immunodeficiency. 15. Has received allogeneic organ transplantation, hematopoietic stem cell transplantation or bone marrow transplantation.

  13. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + chemotherapy	Pemetrexed disodium f Injection	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).
Placebo + chemotherapy	Placebo	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).
Placebo + chemotherapy	Carboplatin injection	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).
Anlotinib hydrochloride capsule + chemotherapy	Carboplatin injection	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).
Anlotinib hydrochloride capsule + chemotherapy	Anlotinib hydrochloride capsule	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).
Anlotinib hydrochloride capsule + chemotherapy	Pemetrexed disodium f Injection	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).

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	up to 48 weeks	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Disease control rate（DCR）	up to 48 weeks	Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).
Overall survival (OS)	up to 48 weeks	OS defined as the time from the first dose to death from any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up.
Disease of Response (DOR)	up to 48 weeks	DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
Overall response rate (ORR) assessed by Independent Review Committee (IRC)	up to 48 weeks	Percentage of subjects achieving complete response (CR) and partial response (PR) based on IRC.

Trial Locations

Locations (59)

The Second Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Anhui Chest Hospital; 🇨🇳 Hefei, Anhui, China

Yijishan Hospital of Wannan Medical College; 🇨🇳 Wuhu, Anhui, China

Beijing Chest Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking University Third Hospital; 🇨🇳 Beijing, Beijing, China

The Sixth Medical Center of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Xuanwu Hospital of Capital Medical University; 🇨🇳 Beijing, Beijing, China

Chinese Academy of Medical Sciences, Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

The Second Affiliated Hospital of Chinese PLA Army Medical University; 🇨🇳 Chongqing, Chongqing, China

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