Combination Tissue Plasminogen Activator (Tpa) and Dornase Alfa (Dnase) Administration Through Intrapleural Catheters for the Treatment of Loculated or Non-Draining Malignant Pleural Effusions

The purpose of this study is to evaluate the efficacy and safety of intrapleural dornase alfa and tPA administered to patients with clinical failure of small-bore chest tube with persistent pleural effusions or malignancy-related loculated effusion to improve pleural drainage.

Study Overview

• Status: Recruiting
• Conditions: Loculated or Non-draining Malignant Pleural Effusions
• Intervention / Treatment: Drug: Combination TISSUE PLASMINOGEN ACTIVATOR (TPA) AND DORNASE ALFA (DNASE)

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Steven B Standiford, MD; Phone Number: 215-537-7400; Email: steven.standiford@ctca-hope.com

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19124
      • Recruiting
      • Eastern Regional Medical Center
      • Contact: Steven B Standiford, MD; Phone Number: 215-537-7400; Email: steven.standiford@ctca-hope.com
      • Principal Investigator: Steven B Standiford, MD
      • Sub-Investigator: Emil Abramian, MD
      • Sub-Investigator: Jeffrey B Hoag, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical failure of small-bore chest tube with persistent pleural effusion
2. 18 years of age or older
3. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2.
4. Life expectancy ≥ 6 weeks
5. Absolute neutrophil count > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.0 g/dL
6. Serum creatinine ≤2.0 times the upper limit of the normal range, total bilirubin ≤ 2.5 mg/dL, AST/ALT ≤ 5 times the upper limit of normal range
7. At least 2 days from administration of chemotherapy
8. At least 7 days from prior major surgery
9. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.
10. Patient judged to be 'medically stable' by primary investigator.

Exclusion Criteria:

1. Prior treatment with intrapleural fibrinolytic agents
2. Presence of any intracranial mass
3. Traumatic hemorrhagic pleural effusion
4. Major hemorrhage, coincidental stroke, or major trauma
5. High-risk for systemic bleeding
6. Allergy or intolerance to dornase alfa
7. Active clinically serious infection > CTCAE (version 4.03) Grade 2.
8. Serious non-healing wound, ulcer, or bone fracture.
9. Major surgery, open biopsy or significant traumatic injury within seven (7) days of first study drug--including neurosurgery.
10. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements.
11. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements.
12. Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test prior to participation in this study)
13. Expected survival less than six weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Treatment; Intra-pleural deoxyribonuclease 5mg and intra-pleural Alteplase 10mg, every 12 hours over 72 hours (total of 6 treatments)	Drug: Combination TISSUE PLASMINOGEN ACTIVATOR (TPA) AND DORNASE ALFA (DNASE)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Radiographic improvement in area of pleural collection	Day 14

Collaborators and Investigators

• Sponsor: Eastern Regional Medical Center
• Investigators: Principal Investigator: Steven B Standiford, MD, Eastern Regional Medical Center, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 8, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimate): May 12, 2014

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: ERMC 13-29