Tocilizumab for Advanced Cancer

(RIOT2 Trial)

Overseen By AHN Clinical Trial Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunotherapy, Investigational drugs

Disqualifiers: Pregnancy, Autoimmune disease, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had active immunotherapy or investigational drugs within 30 days before starting the trial, and concurrent chemotherapy or targeted therapy is allowed.

What data supports the effectiveness of the drug Tocilizumab for advanced cancer?

Tocilizumab is a drug that has been shown to be effective in treating rheumatoid arthritis and juvenile idiopathic arthritis by blocking a protein called interleukin-6 (IL-6) that causes inflammation. While it is not directly studied for advanced cancer, its ability to reduce inflammation might be beneficial in managing cancer-related symptoms. ^{1 2 3 4 5}

How is the drug Tocilizumab unique for treating advanced cancer?

Tocilizumab is unique because it is a monoclonal antibody that targets the interleukin-6 receptor, which is different from many cancer treatments that typically target cancer cells directly. This mechanism is novel for cancer treatment, as Tocilizumab is primarily used for inflammatory conditions like rheumatoid arthritis and juvenile idiopathic arthritis. ^{1 2 3 4 5}

Research Team

Patrick Wagner, MD

Principal Investigator

Director of Complex General Surgical Oncology

Eligibility Criteria

Adults aged 18-89 with metastatic cancer causing fluid buildup in the chest or abdomen can join this trial. They must be able to consent and handle weekly clinic visits. Excluded are those with active infections, recent immunotherapy, pregnancy, known drug allergies, autoimmune diseases, or certain abnormal blood tests.

Inclusion Criteria

I am scheduled for a procedure to drain fluid from my chest or abdomen.

I am able to care for myself and perform daily activities.

I am 18-89 years old with fluid buildup due to cancer spread.

Exclusion Criteria

I am allergic or have had bad reactions to acetaminophen or diphenhydramine.

Your blood tests show significantly high levels of certain indicators like liver enzymes, bilirubin, or creatinine, or low levels of hemoglobin, white blood cells, platelets, or neutrophils.

I cannot follow the study's requirements or travel weekly for clinic visits.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four incremental weekly intra-cavitary doses of tocilizumab

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Tocilizumab

Trial Overview The study is testing if tocilizumab can be safely given directly into the chest or abdominal cavity for patients with malignant ascites or pleural effusions. Participants will receive increasing doses once a week for four weeks through already-planned drainage catheters.

Participant Groups

Group I: Treatment Arm - intracavitary tocilizumab Experimental Treatment 1 Intervention

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.

Tocilizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

52

Recruited

13,000+

Findings from Research

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor, showing efficacy in treating conditions like Castleman disease and various types of arthritis, with approval in Japan and the European Union for these uses.

The drug is currently under review by the US FDA for moderate-to-severe rheumatoid arthritis and has potential applications for other IL-6 related disorders, such as Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab. Venkiteshwaran, A.[2021]

Tocilizumab is an effective treatment for adults with moderate to severe rheumatoid arthritis (RA), showing beneficial effects on disease symptoms and quality of life, based on several large clinical trials and studies.

Long-term use of tocilizumab (up to 9 years) is generally well tolerated, with infections being the most common side effect, and it has been shown to be more effective than adalimumab in patients who cannot continue methotrexate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. Dhillon, S.[2022]

Atlizumab, a humanized monoclonal antibody targeting the interleukin-6 receptor, is being developed for multiple conditions including rheumatoid arthritis and Castleman's disease, highlighting its potential therapeutic efficacy.

The drug has completed phase II development for giant lymph node hyperplasia in Japan and has received orphan drug status, indicating its importance in treating rare diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atlizumab: anti-IL-6 receptor antibody-Chugai, anti-interleukin-6 receptor antibody-Chugai, MRA-Chugai. [2018]

Tocilizumab is an effective treatment for systemic and polyarticular juvenile idiopathic arthritis (JIA) in children aged 2 years and older, showing significant improvement in patient responses compared to placebo in two phase III trials involving patients aged 2-17 years.

The drug was generally well tolerated, with infections being the most common adverse events; however, there was an approximately 11% annual risk of serious infections, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. Frampton, JE.[2021]

Tocilizumab, an IL-6 receptor antagonist, is effective and well tolerated for treating moderate to severe rheumatoid arthritis, showing better results than placebo and other DMARDs in reducing disease activity and improving quality of life.

It is particularly beneficial for patients who have not responded to anti-TNF therapies, making it a valuable option for those with long-standing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the management of rheumatoid arthritis. Oldfield, V., Dhillon, S., Plosker, GL.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tocilizumab. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Atlizumab: anti-IL-6 receptor antibody-Chugai, anti-interleukin-6 receptor antibody-Chugai, MRA-Chugai. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the management of rheumatoid arthritis. [2021]