Clinical trial NCT06016179: Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Advanced Metastatic Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malignant Pleural Effusion
Malignant Ascites
Keywords: Malignant Pleural Effusion
Malignant Ascites
Tocilizumab
IL-6 receptor antagonist
peritoneal cavity
pleural cavity
intraperitoneal
intrapleural
Lead sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor class: OTHER
First posted: 2023-08-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Intra-patient dose escalation administration of tocilizumab via pleural and peritoneal catheters
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Successful intra-cavitary administration of tocilizumab
timeFrame: 6 weeks
measure: Adverse Events
timeFrame: 6 weeks
Secondary outcomes:
measure: Pharmacokinetics Analysis
timeFrame: 4 weeks
measure: Pharmacokinetics Analysis
timeFrame: 4 weeks
measure: Biomarkers
timeFrame: 4 weeks
measure: Biomarkers
timeFrame: 4 weeks
measure: Biomarkers
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Allegheny Health Network Cancer Institute
state: Pennsylvania
Study officials:
affiliation: Director of Complex General Surgical Oncology
name: Patrick Wagner, MD
role: PRINCIPAL_INVESTIGATOR
References: