Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Advanced Metastatic Cancer (RIOT2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Ascites; Malignant Pleural Effusion
• Intervention / Treatment: Drug: Tocilizumab

Detailed 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.

This study is open to patients who have had or are having chest or abdomen drains placed during cancer treatment to relieve pressure due to buildup of cancerous fluid. Some patients have drains that are temporary (single-use), while others have drains that are left in place (indwelling) for repeated or continuous at-home drainage.

Research participants, in addition to the standard treatment above, will undergo a series of four weekly infusions of the study drug into the body cavities, using the drains to inject the drug. The dose of the drug will be increased at each of the four visits. Each treatment session will last about one hour, and participants donate 12 milliliters (1 tablespoon) of blood before and after the treatment.

Fluid drained from the body cavity, which is normally discarded, will instead be collected for analysis. Researchers will analyze the blood and fluid for markers of your immune system's reaction to the drug. The total study duration is expected to be no more than 10 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Patrick Wagner, MD; Phone Number: 412-359-3731; Email: patrick.wagner@ahn.org
• Study Contact Backup: Name: AHN Clinical Trial Contact; Phone Number: 412-359-3731; Email: clinicaltrials@ahn.org

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Allegheny Health Network Cancer Institute
      • Contact: Patrick Wagner, MD; Phone Number: 412-359-3731; Email: patrick.wagner@ahn.org
      • Principal Investigator: Patrick Wagner, MD
      • Sub-Investigator: Catherine Lewis, MD, PhD
      • Sub-Investigator: Stephanie Baltaji, MD
      • Contact: AHN Clinical Trials Contact; Phone Number: 412-359-3731; Email: clinicaltrials@ahn.org
      • Sub-Investigator: David Bartlett, MD
      • Sub-Investigator: Alexander Shannon, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females ages 18-89 years
2. Female patients must have a negative pregnancy test and agree to use contraception. Female patients receiving tocilizumab should maintain adequate contraceptive measures during and for a minimum of 90 days after the last dose of tocilizumab. Male patients receiving tocilizumab should maintain adequate contraceptive measures during and for a minimum of 60 days after the last dose of tocilizumab.
3. Biopsy-proven diagnosis of malignancy with cytologic or radiographic evidence of malignant pleural effusion or ascites
4. Scheduled to undergo standard-of-care pleural or peritoneal drainage catheter placement
5. ECOG 0-2
6. Able to read and understand consent in English and provide informed consent

Exclusion Criteria:

1. Pediatric patients
2. 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 > 2.5 mg/dL Hemoglobin < 7 mg/dL White blood cell count < 3,000/ mm3 Platelet count < 70,000/mm3 Absolute neutrophil cell count < 2,000 per mm3
3. ECOG > 3
4. Subjects who are unable to comply with study procedures including travel for weekly outpatient clinic visits
5. Pregnant and lactating women
6. 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
7. Investigational drug use within 30 days prior to first treatment dose
8. History of systemic autoimmune disease (CRS, GCA, PJIA, RA, and SJIA)
9. Patient with known hypersensitivity to tocilizumab (IL-6)
10. Active infection
11. Medical contraindication or history of adverse reaction to acetaminophen or diphenhydramine

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: Treatment Arm - intracavitary tocilizumab; 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; 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.; Other Names: Actemra

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Investigators: Principal Investigator: Patrick Wagner, MD, Director of Complex General Surgical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 28, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Tocilizumab; intraperitoneal; Malignant Ascites; Malignant Pleural Effusion; intrapleural; IL-6 receptor antagonist; peritoneal cavity; pleural cavity
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Pleural Neoplasms; Pleural Diseases; Neoplasm Metastasis; Pleural Effusion, Malignant; Pleural Effusion; Ascites
• Other Study ID Numbers: 2023-137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No