Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Advanced Metastatic Cancer

Study Overview
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Brief Summary
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The purpose of this study to find out if tocilizumab can be safely infused into chest or abdominal cavities of patients with malignancy ascites (MA) or malignant pleural effusions (MPE). Patients will have a total of 4 doses, one dose administered each week. Each dose will be greater than the previous one.

Detailed Description
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This is an open label, Phase 1, intra-patient dose escalation study to determine the feasibility of catheter-based intra-pleural and intra-peritoneal administration of tocilizumab at doses up to 50μg/mL in patients with malignant pleural effusions (MPE) and malignant ascites (MA) and to determine the frequency and type of adverse events. Tocilizumab is a monoclonal antibody inhibitor of the IL-6 receptor, FDA-approved for intravenous administration in autoimmune disorders and cytokine release syndrome. The current study aims to adapt this agent for intra-cavitary administration in patients A drain catheter will be placed in the patient as standard of care treatment. Following the procedure, on that day and once a week for the following 3 weeks, tocilizumab will be administered to the patient via the drain. Each treatment session will last about one hour, and participants donate 6 milliliters (1 teaspoon) of blood before and after the treatment. Fluid drained from the body cavity, which is normally discarded, will instead be collected for analysis.

Official Title
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Phase I Study of the IL-6 Receptor Antagonist Tocilizumab Delivered Via Pleural and Peritoneal Catheters

Conditions
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Malignant Pleural Effusion, Malignant Ascites

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects age 18-89 years old with pleural effusion or peritoneal ascites due to metastatic cancer Scheduled to undergo standard-of-care placement of pleural or peritoneal drainage catheter ECOG performance status: 0-2 Able to read and sign consent form in English and provide informed consent Exclusion Criteria: Laboratory abnormalities that indicate clinically significant inflammatory process AST/SGOT > 1.5 times the upper limit of normal ALT/SGPT > 1.5 times the upper limit of normal Total bilirubin > 1.5 times the upper limit of normal Creatinine > 1.5 times the upper limit of normal Hemoglobin < 9 gm/dL White blood cell count < 3,000/ mm3 Platelet count < 70,000/mm3 Absolute neutrophil cell count < 2,000 per mm3 Subjects who are unable to comply with study procedures including travel for weekly outpatient clinic visits Pregnant women Active immunotherapy within 30 days; concurrent chemotherapy or targeted therapy is permitted but for patients with a history of prior immunotherapy, the most recent dose should be >30 days prior to the first treatment visit Investigational drug use within 30 days prior to first treatment dose History of systemic autoimmune disease Patient with known hypersensitivity to tocilizumab Active infection Medical contraindication or history of adverse reaction to acetaminophen or diphenhydramine -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Interventional Model Description: Intra-patient dose escalation administration of tocilizumab via pleural and peritoneal catheters
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm - intracavitary tocilizumab<br>Four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks. | Drug: Tocilizumab<br>* Each patient will receive four incremental weekly intra-cavitary doses of tocilizumab starting at 0.5μg/mL and increasing to 1.6μg/mL, 5μg/mL and 50μg/mL once a week over four weeks.<br>* Other names: Actemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful intra-cavitary administration of tocilizumab | Number of patients with successful administration of tocilizumab | 6 weeks | 
| Adverse Events | To identify the frequency and type of adverse events (AE) following intrapleural or intraperitoneal administration of tocilizumab at doses up to 2.5 mg (intrapleural) or 25 mg (intraperitoneal) using CTCAE v5.0 | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Analysis | Measuring serum receptor occupancy levels | 4 weeks | 
| Pharmacokinetics Analysis | Measuring intracavity fluid receptor occupancy levels | 4 weeks | 
| Biomarkers | Change in Pleural cytokine concentrations | 4 weeks | 
| Biomarkers | Change in Peritoneal Cytokine concentrations | 4 weeks | 
| Biomarkers | Change in immune cell density | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant Pleural Effusion, Malignant Ascites, Tocilizumab, IL-6 receptor antagonist, peritoneal cavity, pleural cavity, intraperitoneal, intrapleural