Evaluating Efficacy and Safety of Anlotinib Combined With Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy for Locally Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a prospective, randomized, controlled phase II clinical study for evaluating anlotinib combined with concurrent chemoradiotherapy followed by consolidation immunotherapy versus concurrent chemoradiotherapy followed by consolidation immunotherapy in locally advanced, unresectable NSCLC.

Detailed Description
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This is a prospective, randomized, controlled phase II clinical study for evaluating anlotinib combined with concurrent chemoradiotherapy followed by consolidation immunotherapy versus concurrent chemoradiotherapy followed by consolidation immunotherapy in locally advanced, unresectable NSCLC. In this study, the enrolled patients were divided into the experimental group and the control group at a ratio of 1:1. The patients in the experimental group received anlotinib combined with curative concurrent chemoradiotherapy first, while the patients in the control group received curative concurrent chemoradiotherapy. Those who are evaluated as CR, PR or SD after the aforementioned treatment will enter consolidation immunotherapy. Patients will receive tislelizumab 200mg iv. drip, Q3W, for up to 12 months.

Official Title
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Evaluating Anlotinib Combined With Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy Versus Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy for Locally Advanced Non-small Cell Lung Cancer: A Prospective, Randomized Controlled Phase II Clinical Trial

Conditions
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Locally Advanced Non-small Cell Lung Cancer, Efficacy and Safety

Intervention / Treatment
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* Drug: Anlotinib
* Drug: Chemotherapy
* Radiation: Radiotherapy
* Drug: Immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent is required before proceeding with any steps in the study; Male or female 18-75 years old; Patients must be locally advanced, unresectable (stage IIIA-IIIC) with histology reported NSCLC (except for central squamous cell carcinoma or those at risk for massive hemoptysis); No prior chemotherapy, immunotherapy, radiotherapy, surgery, or targeted therapy; Tumor sample requirements: must provide sufficient evidence to allow analysis Stained, archived tumor tissue samples; Life expectancy ≥ 12 weeks; World Health Organization (WHO) PS score of 0 or 1; Postmenopausal women, or negative urine or serum pregnancy test (HCG) within 14 days prior to study drug administration Women of childbearing potential (WOCBP) must agree to adhere to contraceptive methods during study drug treatment and for 6 months after the last study drug treatment; Men who have sex with WOCBP must agree to adhere to contraception during study drug treatment and for 6 months after the last study drug treatment; azoospermic men do not have to adhere to contraceptive requirements. Adolescents of childbearing potential without heterosexual sex (WOCBP) do not have to comply with contraceptive requirements, but must still undergo a pregnancy test as described in this section; Organ and bone marrow function meet the following conditions: Forced expiratory volume in 1 second (FEV1) ≥ 800ml; Absolute neutrophil count ≥1.5×10^9/L; Platelet ≥100×10^9/L; Hemoglobin ≥9.0g/dL; Serum creatinine clearance calculated according to Cockcroft-Gault formula ≥50 mL/ min (Cockcroft and Gault 1976); Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN); AST and ALT ≤ 2.5 times ULN. Exclusion Criteria: Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study; Histological type of small cell lung cancer (including mixed small cell and non-small cell lung cancer); Prior use of any targeted therapy; The central cavity squamous cell carcinoma or non-small cell lung cancer with hemoptysis (the amount of hemoptysis> 50 ml/d); The patient has conditions that affect oral medication (such as dysphagia, chronic diarrhea, intestinal obstruction, etc.) ; Major surgery (excluding vascular access) within 4 weeks prior to study entry; Heart rate-corrected mean QT interval (QTc) ≥ 470 ms, calculated from 3 electrocardiogram calculation cycles (ECG) using Bazett correction; No Controlled complications, including but not limited to persistent or active infection, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active hemorrhagic Illness, including any known HBsAg-positive patient with HBV DNA > 500 IU/ml, Hepatitis C or Human Immunodeficiency Virus (HIV), or mental illness that would limit compliance with study requirements or impair the patient's ability to give written informed consent/ Social status; History of another primary malignancy within 5 years prior to initiation of therapy, excluding adequately treated skin basal or squamous cell carcinoma or cervical carcinoma in situ; Pregnant, breastfeeding women; Contraceptive method, male or female of reproductive potential; - Conditions that may interfere with the evaluation of the efficacy or safety of the treatment. Patients who progressed after concurrent chemoradiotherapy; History of tuberculosis, excluding old pulmonary tuberculosis; Received live attenuated vaccine within 30 days before study initiation or within 30 days after tislelizide; In Use of immunosuppressive drugs within 28 days prior to the first dose of tislelizumab. Of these, intranasal inhaled corticosteroids at physiological doses are excluded; prednisone or an equivalent amount of systemic corticosteroids not exceeding 10 mg per day is excluded. Steroids are permitted for management of chemoradiotherapy-related toxicity; Patients with unrecovered CTCAE > 2 toxicity after prior targeted combination chemoradiotherapy will be excluded from randomization; due to prior targeted combined chemoradiotherapy, patients with grade ≥2 pneumonitis undergoing chemotherapy will be excluded from randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experiment group<br>Anlotinib Combined With Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy | Drug: Anlotinib<br>* Anlotinib 8mg qd po. Taking anlotinib daily for 2 weeks and stop for 1 week.<br>Drug: Chemotherapy<br>* Docetaxel 25mg/m2 + Cisplatin 25mg/m2 QW<br>* Other names: Concurrent chemoradiotherapy;Radiation: Radiotherapy<br>* Thoracic radiotherapy was delivered using the daily image-guided intensity modulated radiation therapy (IMRT) technique. The total radiation dose was 66-68 Gy to the gross tumor in 17-22 daily fractions.<br>* Other names: Concurrent chemoradiotherapy;Drug: Immunotherapy<br>* consolidation Immunotherapy (Tislelizhu 200mg iv. drip, Q3W, up to 12 months.)<br>|
| Active Comparator: Control group<br>Concurrent Chemoradiotherapy Followed by Consolidation Immunotherapy | Drug: Chemotherapy<br>* Docetaxel 25mg/m2 + Cisplatin 25mg/m2 QW<br>* Other names: Concurrent chemoradiotherapy;Radiation: Radiotherapy<br>* Thoracic radiotherapy was delivered using the daily image-guided intensity modulated radiation therapy (IMRT) technique. The total radiation dose was 66-68 Gy to the gross tumor in 17-22 daily fractions.<br>* Other names: Concurrent chemoradiotherapy;Drug: Immunotherapy<br>* consolidation Immunotherapy (Tislelizhu 200mg iv. drip, Q3W, up to 12 months.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18-months progression-free survival rate | From the first day of treatment to the day of progression or the day of death. | 18-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | It was calculated from the first day of treatment to the day of death. | 18-months | 
| objective response rate | The proportion patients evaluated for CR and PR | 18-months | 
| Incidence of Treatment-related Adverse Events | Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on. | 18 months after therapy | 
| Score of EORTC QLQ-C30 | The evaluation of life quality | 18 months after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced non-small cell lung cancer, Anlotinib combined with chemoradiotherapy, Consolidation immunotherapy