Combined Simvastatin and Albumin Paclitaxel in Treating ES-SCLC Patients Relapsed From 1st Chemotherapy

Study Overview
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Brief Summary
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This Phase II study was designed to evaluate the safety and efficacy of albumin paclitaxel in combination with simvastatin compared with treatment with albumin paclitaxel alone in ES-SCLC patients relapsed from first-line chemotherapy. Participants will be divided in a 1:1 ratio to receive either albumin paclitaxel (4 cycles) + simvastatin (10 months) or albumin paclitaxel (4 cycles) until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or symptomatic deterioration.

Detailed Description
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PRIMARY OBJECTIVES: I.To assess disease control rate (DCR) after treatment. SECONDARY OBJECTIVES: I.To assess best overall response rate (ORR) after treatment. II.To evaluate the progression-free survival (PFS) of patients with extensive stage-small cell lung cancer (ES-SCLC) treated with albumin paclitaxel + simvastatin or with albumin paclitaxel alone. III.To estimate overall survival (OS) of patients with ES-SCLC. IV. To evaluate the toxicity profile of albumin paclitaxel + simvastatin. EXPLORATORY OBJECTIVES: I.To evaluate biomarkers correlatives. II.To explore the mechanism of albumin paclitaxel + simvastatin in the treatment of chemotherapy-resistant participants with ES-SCLC. OUTLINE: Patients are divided into two arms. ARM A: Participants received intravenous infusions of albumin paclitaxel 260 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle in combination with oral simvastatin (20mg daily) until persistent radiographic PD as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or symptomatic deterioration. ARM B:Participants received intravenous infusions of albumin paclitaxel 260 mg/m^2 alone on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Official Title
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Clinical Study of Albumin Paclitaxel With or Without Simvastatin in Treating Extensive-Stage Small Cell Lung Cancer Patients Relapsed From First-line Chemotherapy

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Albumin Paclitaxel
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be volunteered to participate in the clinical trial. Patients must sign the informed Consent form (ICF) and be willing to follow and be able to complete all test procedures. Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system). No patients with resectable or radical radiotherapy lung cancer. Patient must have no Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic lymphoma kinase (ALK) rearrangement, or ROS proto-oncogene 1 , receptor tyrosine kinase(ROS1) rearrangement. Patient must be at least resistant to the first-line chemotherapy. Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients can tolerate chemotherapy. Exclusion Criteria: Unclear diagnosis of SCLC. Resectable or radical radiotherapy SCLC. Contraindicated chemotherapy. Undergoing other active malignancies within 5 years or at the same time.Patients with localized curable tumors, such as basal cell carcinoma, squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ, will not be excluded. Positive test result for human immunodeficiency virus (HIV). Positive test result for active tuberculosis. Live vaccine was administered within 28 days of initial administration. Inactivated viral vaccines for seasonal influenza are allowed, except for live attenuated intranasal vaccines. Pregnant or lactating women. A history of psychotropic substance abuse, drug abuse, or alcoholism. Other factors assessed by the sponsors.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin + Albumin Paclitaxel<br>received intravenous infusions of Paclitaxel 260 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle (4 cycles) in combination with oral simvastatin (20mg daily) (10 months) | Drug: Albumin Paclitaxel<br>* Albumin Paclitaxel intravenous infusion was administered at a dose of 260 mg/m^2 on Day 1 of each 21-day cycle.<br>Drug: Simvastatin<br>* 20mg daily oral tablet taken.<br>* Other names: Simvastatin Tablets;|
| Active Comparator: Albumin Paclitaxel<br>received intravenous infusions of Paclitaxel 260 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle (4 cycles) | Drug: Albumin Paclitaxel<br>* Albumin Paclitaxel intravenous infusion was administered at a dose of 260 mg/m^2 on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | To assess disease control rate (DCR) after treatment. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | To assess best overall response rate (ORR) after treatment. | 6 weeks | 
| Progression-free survival (PFS) | To evaluate the progression-free survival (PFS) of patients with extensive stage small cell lung cancer (ES-SCLC) treated with paclitaxel + simvastatin or with paclitaxel alone. | 12 weeks | 
| Overall survival (OS) | To estimate overall survival (OS) of patients with ES-SCLC. | 24 weeks | 
| Number of participants with treatment-related adverse events (AE) as assessed by CTCAE v4.0 | To evaluate the toxicity profile. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ES-SCLC, Chemo-resistance, Simvastatin