Split-course Thoracic Radiotherapy Combined With Nab-paclitaxel Plus Nedaplatin for Local Advanced NSCLC With Impaired Baseline Pulmonary Function

Study Overview
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Brief Summary
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This Phase II randomized study is to determine the efficacy of split-course thoracic radiotherapy combined with nab-paclitaxel plus nedaplatin for local advanced non-small cell lung cancer with severe impairment of baseline pulmonary function.

Detailed Description
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This Phase II randomized study is to determine the efficacy of split-course thoracic radiotherapy combined with nab-paclitaxel plus nedaplatin for local advanced non-small cell lung cancer with severe impairment of baseline pulmonary function. Patients received four cycles of weekly nab-paclitaxel(50mg/㎡) and nedaplatin(25mg/㎡), each of 1 day's duration, or nab-paclitaxel(30mg/㎡) and nedaplatin(10mg/㎡) twice every week, concurrent with split-course thoracic radiotherapy of 30 Gy/6 fractions and 40 Gy/8 fractions administered in the first and second courses, respectively, with one-month break. The primary end point is progression-free survival, which is the time that passes from the first day of radiotherapy to the date at which disease progresses. Progression-free survival will be calculated using the Kaplan-Meier method.Toxicities will be graded according to CTCAE v. 4.0.

Official Title
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Split-course Thoracic Radiotherapy Combined With Nab-paclitaxel Plus Nedaplatin for Local Advanced NSCLC With Impaired Baseline Pulmonary Function

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: split-course radiotherapy
* Drug: concurrent chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic confirmation of NSCLC. Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Moderate to severe obstructive ventilatory dysfunction (FEV1.0/FVC≤60%), or / and moderate to severe restrictive ventilatory dysfunction(FEV1.0/FVC≤60%，TLC-SB（Act1/Pred）≤80%), or / and moderate to severe diffusion dysfunction (DLCOc/VA（Act1/Pred）≤60%). Unresectable phase IIIA(N2) and IIIB lung cancer confirmed by EBUS. Whole lung V20>=35% when giving 60Gy which is the minimum dose of radical irradiation. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Previously treated with chemotherapy or treatment-naive No previous chest radiotherapy, immunotherapy or biotherapy Hemoglobin≥10 mg/dL, platelet≥100000/μL,absolute neutrophil count ≥1500/μL Serum creatinine ≤1.25 times the upper normal limit(UNL), or creatinine clearance≥60 ml/min Bilirubin ≤1.5 times UNL, AST（SGOT）≤2.5 times UNL ,ALT（SGPT）≤2.5 times UNL,alkaline phosphatase ≤5 times UNL CB6 within normal limits patients and their family signed the informed consents Exclusion Criteria: Previous or recent another malignancy, except nonmelanoma skin cancer or cervical cancer in situ Contraindication for chemotherapy Malignant pleural or pericardial effusion. Women in pregnancy, lactation period, or no pregnancy test 14 days before the first dose Women who has the probability of pregnancy without contraception Tendency of hemorrhage In other clinical trials within 30 days Addicted in drugs or alcohol, AIDS patients Uncontrollable seizure or psychotic patients without self-control ability Severe allergy or idiosyncrasy Not suitable for this study judged by researchers

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: split-course radiotherapy<br>The radiotherapy is delivered using simultaneous integrated boost (SIB)-intensity-modulated radiotherapy (IMRT). Patients are irradiation at a palliative dose at the initial course: 30Gy/6f to gross tumor. The disease is re-evaluated one month after the end of the initial course using CT. The patient who achieved a partial remission according to the RECIST criteria and had a recovery of lung function should get the additional boost. At the second course, the tumor is re-simulated. The residual tumor was then treated with the second course of radiotherapy. A dose of 40Gy/8f is delivered to the residue tumor. Concurrent chemotherapy consists of weekly nab-paclitaxel(50mg/㎡) and nedaplatin(25mg/㎡), each of 1 day's duration, or nab-paclitaxel(30mg/㎡) and nedaplatin(10mg/㎡) twice every week. | Radiation: split-course radiotherapy<br>* Patients are irradiation at a palliative dose at the initial course: 30Gy/6f to PTV-GTV. The disease is re-evaluated one month after the end of the initial course using CT. The patient who achieved a partial remission according to the RECIST criteria and had a recovery of lung function should get the additional boost. At the second course, the tumor is repositioned and scanned. The residual tumor was then treated with the second course of radiotherapy. A dose of 40Gy/8f is delivered to the residue tumor.<br>Drug: concurrent chemotherapy<br>* Concurrent chemotherapy consists of weekly nab-paclitaxel(50mg/㎡) and nedaplatin(25mg/㎡), each of 1 day's duration, or nab-paclitaxel(30mg/㎡) and nedaplatin(10mg/㎡) twice every week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 3 years | 
| response rate |  | 2 months | 
| rate of grade 3-4 radiation esophagitis |  | 1 year | 
| rate of grade 3-4 radiation pneumonitis |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, Split-course radiotherapy, Severe Impairment of Baseline Pulmonary Function, Nab-paclitaxel