Safety and Effectiveness of MPCD Therapy on the Treatment of Malignant Pleural Effusion

Study Overview
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Brief Summary
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This is a prospective, open-label , multicenter randomized controlled trial, with 248 cases in 50 centers planned for a period of 2 years. The aim of the study is to evaluate the safety and effectiveness of microparticles packaging chemotherapeutic drugs (MPCD) therapy on the treatment of malignant pleural effusion (MPE) in patients with advanced lung cancer or breast cancer.

Detailed Description
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After obtaining informed consent, patients who meet the eligibility criteria will be randomly assigned 1:1 to treatment either with MPCD or recombinant human interleukin-2(rhIL-2) for injection. Randomization is stratified by tumor type and previous treatment. Patients in the MPCD group are first treated with microparticles packaging methotrexate (MPs-MTX) via intrapleural infusion four times on day5,6,7,8 and then undergo chemotherapy 1 cycle from day12. Patients in the control group are first treated with rhIL-2 via intrapleural infusion three times on day5,8,11 and then undergo chemotherapy 1 cycle from day12. After 4 weeks from the beginning of the treatment (day1 of treatment), the efficacy is assessed according to the WHO (1997) Response Evaluation Criteria In MPE and the evaluation methods mainly include physical examination, ultrasound and computed tomography (CT). The patients will be monitored by telephone every three months.

Official Title
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Safety and Effectiveness of Microparticles Packaging Chemotherapeutic Drugs(MPCD) Therapy on the Treatment of Malignant Pleural Effusion

Conditions
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Lung Cancer, Breast Cancer, Malignant Pleural Effusion

Intervention / Treatment
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* Drug: microparticles packaging methotrexate (MPs-MTX)
* Drug: recombinant human interleukin-2(rhIL-2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed as lung cancer or breast cancer; Cytologically or histologically confirmed MPE needing thoracocentesis treatment; Without thoracocentesis treatment within 4 weeks; ECOG PS score: 0-2 points; Predicted life expectancy greater than 3 months; 18 years ≤Age ≤80 years； Bone marrow function: hemoglobin(HGB) ≥90g/L，white blood cells(WBC) ≥3.0×10^9/L，absolute neutrophil count(ANC) ≥1.5×10^9/L，platelets (PLT) ≥80×10^9/L，international standardized ratio (INR) <1.5; Hepatic function：alanine aminotransferase(ALT) and aspartate aminotransferase(AST) ≤2.5×ULN，serum total bilirubin≤1.5× ULN; Renal function：blood urea nitrogen(BUN) and serum creatinine(Cr) ≤1.5×ULN, or endogenous creatinine clearance rate(Ccr) ≥60mL/min; Without other severe cardiac disease or respiratory disease; The volunteers voluntarily join the study, sign informed consent, and have good compliance and follow-up. Exclusion Criteria: Inappropriate to receive chemotherapy; Women who are pregnant, preparing to be pregnant, breastfeeding; Known or suspected hypersusceptibility to any agents used in the treatment protocol; With severe cardiac disease, respiratory disease, liver disease, kidney disease, or diabetes; With severe infection; With severe encapsulated pleural effusion or intrathoracic tissue adhesion which is inappropriate to receive thoracocentesis; With cognitive impairment or low compliance; Participating in other clinical trials within 4 weeks; Undergoing immunotherapy within 3 months; Other conditions considered to be inappropriate to be enrolled by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: microparticles packaging methotrexate (MPs-MTX) group<br>Patients are first treated with microparticles packaging methotrexate (MPs-MTX) via intrapleural infusion four times on day5,6,7,8 and then undergo chemotherapy 1 cycle from day12. After 4 weeks from the beginning of the treatment (day1 of treatment), ORR is assessed. MPs-MTX: 5 U of MPs-MTX containing a total dose of more than 25μg of MTX dissolving in 50ml of physiological saline solution | Drug: microparticles packaging methotrexate (MPs-MTX)<br>* 50ml, intrapleural infusion, day5,6,7,8<br>|
| Active Comparator: recombinant human interleukin-2(rhIL-2) group<br>Patients are first treated with rhIL-2 via intrapleural infusion three times on day5,8,11 and then undergo chemotherapy 1 cycle from day12. After 4 weeks from the beginning of the treatment (day1 of treatment), ORR is assessed. rhIL-2: 2 million IU of rhIL-2 dissolving in 50ml of physiological saline solution | Drug: recombinant human interleukin-2(rhIL-2)<br>* 50ml, intrapleural infusion, day5,8,11<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate（ORR） | Percentage of patients whose pleural effusion completely recover or reduce by more than 50% for more than 4 weeks | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Time from the date of first receive treatment to the date of first documented progression or date of death from any cause whichever came first | up to 20 months | 
| Overall Survival(OS) | Time from the date of first receive treatment to the date of death | up to 20 months | 
| Level of tumor markers | The change of the level of tumor markers(CEA,CA125) in blood and pleural effusion before and after treatment | up to 20 months | 
| Index of pleural effusion | Routine, biochemistry and cytological examination of pleural effusion | up to 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPE, microparticles packaging chemotherapeutic drugs, MPCD, malignant pleural effusion