The Efficacy and Safety of Nanoparticle Albumin-bound (NAB)-Paclitaxel Plus Cisolation Versus CEP (Cisplatin, Epirubicin,Cyclophosphamide) in Induction Therapy for Thymoma: a Study for a Single-center Prospective Phase II Randomized Controlled Train.

Study Overview
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Brief Summary
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This study for a single-center prospective phase II randomized controlled train to assess the efficacy and safety of Induction therapy on thymoma .Methods patients with thymoma (stage Ⅲ and stage Ⅳa) were treated with 2 cycles of (NAB)-paclitaxel plus Cisolation (Paclitaxel For Injection(Aalbumin Bound）125 mg/m2 Day 1 、Day8 ,Cisplatin 75 mg/m2 Day 1of each 3-week cycle）or CEP(cisplatin 50 mg/m2 Day 1, epirubicin 75 mg/m2 Day 1,cyclophosphamide 500 mg/m2 Day 1 of each 3-week cycle). Following chemotherapy to evaluate the patient for operation. Patients without undergo surgery will be continued to receive 2 cycles of Primary chemotherap.

Official Title
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The Efficacy and Safety of Nanoparticle Albumin-bound (NAB)-Paclitaxel Plus Cisolation Versus CEP (Cisplatin, Epirubicin,Cyclophosphamide) in Induction Therapy for Thymoma: a Study for a Single-center Prospective Phase II Randomized Controlled Train.

Conditions
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Histological or Cytological Confirmed Stage Ⅲ and Ⅳa Thymoma

Intervention / Treatment
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* Drug: NAB-Paclitaxel plus Cisplatin
* Drug: Cisplatin plus Epirubicin plus Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years； Histological or cytological confirmed stage Ⅲ and Ⅳa thymoma; PET/CT or CT/MRI with at least one objectively measurable or evaluable lesion； Life expectancy >12months； ECOG PS 0-1； --Patients with thymoma metastasis； No found the other malignant tumors (expect has been controlled Carcinoma in situ of the cervix and Basal Cell Carcinoma）； Informed consent was signed before the study began； Normal Bone marrow hematopoiesis and renal function，Blood routine: absolute neutrophil count≥1,500/uL，Hb>8.0g/dL，PLT>80×10*9/L，AST≤ 1.5 times the upper limit of normal，TBIL ≤1.5 times the upper limit of normal，calculated creatinine clearance ≤110µmol/L，blood urea nitrogen≤7.1mmol/L； Cardiac function: LVEF≥55%； Patients who have not active bleeding or coagulopathy before enrollment； Exclusion Criteria: -Patients who have been found thymoma metastasis； Patients with uncontrolled lung disease, Serious infection,active peptic ulcers, coagulation diaorders, Uncontrolled severe diabetes, connective tissue diseases or Bone marrow suppression and Induction therapy for intolerance； Peripheral neuropathy ≥ Grade 2 (NCI-CTCAE version 5.0 )； Significant organ dysfunction: such as respiratory failure, NYHA classification Class III or IV, chronic congestive heart failure, decompensation Hepatic or renal insufficiency, high blood pressure（SBP> 180 mmHg or DBP> 100mmHg）； Pregnant and lactating women； patients without undergo preoperative puncture biopsy or induction therapy； Patients with active uncontrollable neurological, mental disease or mental disorder, poor compliance, unable to cooperate and describe the treatment response； Patients who have received any other investigational drug treatment or participated in any other clinical trials within 30 days prior to enrollment in this study； Known HIV infection or active infection with HBV, HCV. Patients who are infected with HBV but not active hepatitis at the same time are not excluded； Patients with uncontrollable Stable myasthenia gravis or uncontrollable Serious autoimmune disease such as fulminant DIC； Patients who are known to be allergic or intolerant to chemotherapy drugs； severe-trauma； Patients who have received any other investigational drug treatment or participated in any other clinical trials within 30 days prior to enrollment in this study；

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CEP<br>Cisplatin was administered as 50 mg/m2 IV infusion on Day 1; Epirubicin was administered as 75 mg/m2 IV infusion on Day 1; Cyclophosphamide was administered as 500 mg/m2IV infusion on Day 1 of each 3-week cycle.Patients will receive maximum of 4 cycles if they do not meet the criteria for removal from the study. | Drug: Cisplatin plus Epirubicin plus Cyclophosphamide<br>* Cisplatin was administered as 50 mg/m2 IV infusion on Day 1; Epirubicin was administered as 75 mg/m2 IV infusion on Day 1; Cyclophosphamide was administered as 500 mg/m2IV infusion on Day 1 of each 3-week cycle.Patients will receive maximum of 4 cycles if they do not meet the criteria for removal from the study.<br>|
| Experimental: NAB-Paclitaxel<br>NAB-Paclitaxel will be administered as 125 mg/m2 IV infusion on Day 1 、Day8 of each 3-week cycle. Cisplatin will be administered as 75 mg/m2 IV infusion on Day 1 of each 3-week cycle. Patients will receive maximum of 4 cycles if they do not meet the criteria for removal from the study. | Drug: NAB-Paclitaxel plus Cisplatin<br>* NAB-Paclitaxel will be administered as 125 mg/m2 IV infusion on Day 1 、Day8 of each 3-week cycle. Cisplatin will be administered as 75 mg/m2 IV infusion on Day 1 of each 3-week cycle. Patients will receive maximum of 4 cycles if they do not meet the criteria for removal from the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) | the proportion of patients with complete response and partial response , using RECIST v 1.1 | assessed up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease free survival (3yr-DFS) | the percentage of Primary thymoma patients without recurrence/metastasis within 3 years in all enrolled patients | assessed up to 3 year | 
| overall survival rate (OS) | from date of enrolment to date of death of any reason | assessed up to 3 year | 
| Incidence of adverse events |  | assessed up to 1 year | 
| Surgical conversion success rate | Following chemotherapy to evaluate proportion of patients underwent timely operation | assessed up to 1 year | 
| Pathologic Complete Response（pCR） | the proportion of patients with complete response , using RECIST v 1.1 | assessed up to 1 year | 
| Main pathological Response | the proportion of patients with complete response and partial response , using RECIST v 1.1 | assessed up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymoma, nanoparticle albumin-bound (NAB)-paclitaxel plus Cisolation, CEP (cisplatin, epirubicin,cyclophosphamide)