Endostar in Combination With Chemoradiotherapy in Patient With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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To investigate the safety and efficacy recombinant human endostatin(endostar) durative transfusion combined with cocurrent chemoradiotherapy in advanced non-small cell lung cancer(NSCLC).

Official Title
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Recombinant Human Endostatin (Endostar) Combined With Concurrent Chemoradiotherapy for Advanced Non-small Cell Lung Cancer: A Multicenter, Randomized, Controlled Trial

Conditions
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Quality of Life

Intervention / Treatment
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* Combination Product: concurrent chemoradiotherapy (CCRT)
* Drug: Endostar for one cycle
* Drug: Endostar for two cycles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male or female patients, age: 18-70 years of age 2. Pathology was diagnosed as non-small cell lung cancer. According to the Tumor Node Metastasis（TNM）stage of the 8th edition of the International Association for the Study of Lung Cancer in 2017, And the pathological stage was identified as stage IIIa-b. 3. No previous chest radiotherapy and radiotherapy, immunotherapy or biological therapy. 4. Eastern Cooperative Oncology Group (ECOG) test scored 0-1. 5. Serum hemoglobin ≥ 100g/L, platelet ≥ 100 × 109/L, absolute number of neutrophils ≥ 1.5 × 109/L. 6. Serum creatinine ≤ 1.25 times the upper limit of normal(UNL) or creatinine clearance ≥ 60 mL/min. 7. Serum bilirubin ≤ 1.5 times UNL, Aspartate aminotransferase (AST) and adenosine triphosphate (ALT) ≤ 2.5 times UNL, alkaline phosphatase ≤ 5 times UNL. 8. Forced vital capacity rate of one second（FEV1）>0.8 litre. 9. Coagulation function is normal 10. lesions are measurable according to the Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST1.1)standard 11. Sign the inform consent form with good compliance Exclusion Criteria: 1. Carcinoid or small cell lung cancer 2. Patients with any distant metastasis 3. patients with previous or current malignancy, except for skin non-melanoma or carcinoma in situ in the cervix 4. Any other disease or condition is a contraindication to chemoradiation (eg, active infection, 6 months after myocardial infarction, symptomatic heart disease including unstable angina, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy). 5. Pregnancy or breastfeeding women 6. Women who may be pregnant but are unwilling to take appropriate contraception 7. Hereditary bleeding or coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Interventional Model Description: Patients were randomly assigned to a regimen of W1-CCRT(one treatment cycle of intravenous pump of recombinant human endostatin before chemoradiotherapy), or W2-CCRT(two treatment cycle of intravenous pump of recombinant human endostatin before chemoradiotherapy), or CCRT.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: concurrent chemoradiotherapy (CCRT)<br>Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed. | Combination Product: concurrent chemoradiotherapy (CCRT)<br>* Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed.<br>|
| Experimental: W1-CCRT<br>Endostar(15 mg/m2) was durative transfused every 24 hours for 5 days during the normalization window of the first chemoradiotherapy cycle(days -5～-1). Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed. | Combination Product: concurrent chemoradiotherapy (CCRT)<br>* Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed.<br>Drug: Endostar for one cycle<br>* Endostar(15mg/m2) was durative transfused during the normalization window of the first chemoradiotherapy cycle(days -5～-1).<br>|
| Experimental: W2-CCRT<br>Endostar(15 mg/m2) was durative transfused every 24 hours for 5 days during the normalization window of the first and the second chemoradiotherapy cycles(days -5～-1 and 24～28). Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed. | Combination Product: concurrent chemoradiotherapy (CCRT)<br>* Chemotherapy: Cisplatin (50 mg/m2) on days 1, 8, 29, and 36 and etoposide (50mg/m2) on days 1～5 and 29～33. Radiotherapy: Thoracic radiotherapy (TRT) started with a linear accelerator (6MV-X) on the first day of chemotherapy.A minimum dose of 60 Gy (2 Gy per fraction, Monday～Friday) was delivered, and a range of 60-66 Gy in 2 Gy fractions was allowed.<br>Drug: Endostar for two cycles<br>* Endostar(15mg/m2) was durative transfused during the normalization window of the first and the second chemoradiotherapy cycles(days -5～-1 and 24～28).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS) | Evaluate the effect of chemoradiotherapy with or without recombinant human endostatin on progression free survival | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival(OS) | comparison to maintenance chemoradiotherapy alone | 4 years | 
| Treatment-related toxicity | Toxicity and adverse events related to the inventions | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant human endostatin, NSCLC, chemoradiotherapy