Recombinant Human Endostatin Continued Pumping Into Vein Combining With CCRT in Unresectable Stage III NSCLC

Study Overview
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Brief Summary
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Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors, especially the squamous cell carcinomas. Preclinical models have shown that Endostar may transiently normalize the tumor vasculature to make it more efficient for oxygen delivery, thereby providing a window of opportunity for enhanced sensitivity to radiation treatment. This study is to evaluate the safety, toxicity, and efficacy of the addition of Endostar Continued Pumping into Vein to the standard CCRT regimen in patients with unresectable stage III NSCLC.

Detailed Description
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Primary Evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC). Secondary Measure changes in VEGF and other angiogenic cytokines and antiangiogenic factors in plasma samples from these patients. Evaluate the application of CT perfusion imaging to determine changes in tumor vascular mophology and function during treatment.

Official Title
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Multicenter Phase I/II Clinical Trial of Recombinant Human Endostatin Continued Pumping Into Vein Combining With Concurrent Chemo-Radiotherapy in the Patients With Unresectable Stage III Non-small-Cell Lung Cancer

Conditions
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Stage III Non-small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Recombinant human endostatin
* Drug: Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles
* Drug: cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles
* Other: laboratory biomarker analysis
* Other: CT perfusion imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: untreated histologic or cytologic of NSCLC verified inoperable stage IIIA or IIIB NSCLC measurable disease by RECIST 18 70 years of age an ECOG PS of 0 to 1 absolute neutrophil count (ANC) of ≥1500/μL, hemoglobin ≥10gm/dL, platelet ≥100,000/μL serum creatinine ≤1.25 times of upper limit of normal (ULN), calculated creatinine clearance (CrCl) of ≥60ml/min bilirubin 1.5×ULN, AST and ALT less than 2.5×ULN, alkaline phosphatase less than 5×ULN forced vital capacity in 1 second (FEV1) higher than 0.8 L CB6 is normal Written informed consent Exclusion Criteria: a history of other malignant diseases any contraindications for chemoradiotherapy distant metastasis malignant pleural and/or pericardial effusion pregnant or nursing preexisting bleeding diatheses 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant Human Endostatin<br>All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60 66Gy in 30 33 fractions for 6 7 weeks. | Drug: Recombinant human endostatin<br>* Recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7,combined with concurrent chemo-radiotherapy.<br>Drug: Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles<br> <br> Drug: cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles<br> <br> Other: laboratory biomarker analysis<br> <br> Other: CT perfusion imaging<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | from beginning treatment to progressive disease or the last follow-up | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | complete response(CR); partial response(PR); stable disease(SD); progressive disease(PD) | 1 month | 
| overall survival | from date of beginning treatment until date of death | 5 years | 
| treatment related toxicities | radiation-induced esophagitis; radiation-induced pneumonia | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant human endostatin, Non-small-Cell Lung Cancer, chemoradiotherapy