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

Malignant Pleural Effusion Clinical Trial

— RIOT2  

Official title:

Phase I Intra-patient Dose Escalation Study of the IL-6 Receptor Antagonist Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Pleural Effusion or Peritoneal Ascites Due to Metastatic Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06016179
• Other study ID #: 2023-137
• Status: Recruiting
• Phase: Phase 1
• Start date: January 30, 2024
• Est. completion date: January 2027

Study information

• Verified date: March 2024
• Source: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Contact: Patrick Wagner, MD
• Phone: 412-359-3731
• Email: patrick.wagner[@]ahn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

1. Subjects age 18-89 years old with pleural effusion or peritoneal ascites due to metastatic cancer

2. Scheduled to undergo standard-of-care placement of pleural or peritoneal drainage catheter

3. ECOG performance status: 0-2

4. Able to read and sign consent form in English and provide informed consent

Exclusion Criteria:

1. Laboratory abnormalities that indicate clinically significant inflammatory process AST/SGOT > 2 times the upper limit of normal ALT/SGPT > 2 times the upper limit of normal Total bilirubin > 2 times the upper limit of normal Creatinine > 2 times the upper limit of normal Hemoglobin < 8gm/dL White blood cell count < 3,000/ mm3 Platelet count < 70,000/mm3 Absolute neutrophil cell count < 2,000 per mm3

2. Subjects who are unable to comply with study procedures including travel for weekly outpatient clinic visits

3. Pregnant women

4. 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

5. Investigational drug use within 30 days prior to first treatment dose

6. History of systemic autoimmune disease

7. Patient with known hypersensitivity to tocilizumab

8. Active infection

9. Medical contraindication or history of adverse reaction to acetaminophen or diphenhydramine

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Related Conditions & MeSH terms

• Ascites
• Malignant Ascites
• Malignant Pleural Effusion
• Neoplasm Metastasis
• Pleural Effusion
• Pleural Effusion, Malignant

Intervention

Drug:
• Tocilizumab
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.

Locations

Country	Name	City	State
United States	Allegheny Health Network Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Successful intra-cavitary administration of tocilizumab	Number of patients with successful administration of tocilizumab	6 weeks
Primary	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	Pharmacokinetics Analysis	Measuring serum receptor occupancy levels	4 weeks
Secondary	Pharmacokinetics Analysis	Measuring intracavity fluid receptor occupancy levels	4 weeks
Secondary	Biomarkers	Change in Pleural cytokine concentrations	4 weeks
Secondary	Biomarkers	Change in Peritoneal Cytokine concentrations	4 weeks
Secondary	Biomarkers	Change in immune cell density	4 weeks