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

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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Lung Cancer; Malignant Pleural Effusion
• Intervention / Treatment: Drug: microparticles packaging methotrexate (MPs-MTX); Drug: recombinant human interleukin-2(rhIL-2)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 248
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed as lung cancer or breast cancer;
2. Cytologically or histologically confirmed MPE needing thoracocentesis treatment;
3. Without thoracocentesis treatment within 4 weeks;
4. ECOG PS score: 0-2 points;
5. Predicted life expectancy greater than 3 months;
6. 18 years ≤Age ≤80 years；
7. 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;
8. Hepatic function：alanine aminotransferase(ALT) and aspartate aminotransferase(AST) ≤2.5×ULN，serum total bilirubin≤1.5× ULN;
9. Renal function：blood urea nitrogen(BUN) and serum creatinine(Cr) ≤1.5×ULN, or endogenous creatinine clearance rate(Ccr) ≥60mL/min;
10. Without other severe cardiac disease or respiratory disease;
11. The volunteers voluntarily join the study, sign informed consent, and have good compliance and follow-up.

Exclusion Criteria:

1. Inappropriate to receive chemotherapy;
2. Women who are pregnant, preparing to be pregnant, breastfeeding;
3. Known or suspected hypersusceptibility to any agents used in the treatment protocol;
4. With severe cardiac disease, respiratory disease, liver disease, kidney disease, or diabetes;
5. With severe infection;
6. With severe encapsulated pleural effusion or intrathoracic tissue adhesion which is inappropriate to receive thoracocentesis;
7. With cognitive impairment or low compliance;
8. Participating in other clinical trials within 4 weeks;
9. Undergoing immunotherapy within 3 months;
10. Other conditions considered to be inappropriate to be enrolled by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: microparticles packaging methotrexate (MPs-MTX) group; 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); 50ml, intrapleural infusion, day5,6,7,8
ACTIVE_COMPARATOR: recombinant human interleukin-2(rhIL-2) group; 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); 50ml, intrapleural infusion, day5,8,11

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 15, 2019
• Primary Completion (ANTICIPATED): January 15, 2021
• Study Completion (ANTICIPATED): June 15, 2021

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 16, 2019
• First Posted (ACTUAL): October 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: malignant pleural effusion; MPE; microparticles packaging chemotherapeutic drugs; MPCD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Aldesleukin; Methotrexate; Interleukin-2
• Other Study ID Numbers: NCC20180327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No