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

Sponsor

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06016179

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Effusion Malignant Ascites	Drug: Tocilizumab	Phase 1

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Intra-patient dose escalation administration of tocilizumab via pleural and peritoneal cathetersIntra-patient dose escalation administration of tocilizumab via pleural and peritoneal catheters

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Successful intra-cavitary administration of tocilizumab [6 weeks]
Number of patients with successful administration of tocilizumab
Adverse Events [6 weeks]
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

Secondary Outcome Measures

Pharmacokinetics Analysis [4 weeks]
Measuring serum receptor occupancy levels
Pharmacokinetics Analysis [4 weeks]
Measuring intracavity fluid receptor occupancy levels
Biomarkers [4 weeks]
Change in Pleural cytokine concentrations
Biomarkers [4 weeks]
Change in Peritoneal Cytokine concentrations
Biomarkers [4 weeks]
Change in immune cell density

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allegheny Health Network Cancer Institute	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Patrick Wagner, MD, FACS, Investigator, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

ClinicalTrials.gov Identifier:

NCT06016179

Other Study ID Numbers:

2023-137

First Posted:

Aug 29, 2023

Last Update Posted:

Sep 1, 2023

Last Verified:

Aug 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Patrick Wagner, MD, FACS, Investigator, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Malignant Pleural Effusion

Malignant Ascites

Tocilizumab

IL-6 receptor antagonist

Additional relevant MeSH terms:

Pleural Effusion, Malignant

Pleural Effusion

Ascites

Study Results

No Results Posted as of Sep 1, 2023