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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether tocilizumab, an immunosuppressive drug, can be safely used in patients with fluid buildup in the chest or abdomen due to advanced cancer. Tocilizumab is infused directly into these areas, with doses increasing over four weeks. It targets patients diagnosed with cancer who have fluid in the chest or abdomen requiring drainage. The goal is to determine the safety of this treatment approach. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

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.

Is there any evidence suggesting that tocilizumab is likely to be safe for humans?

Research has shown that tocilizumab has been studied for its safety in treating various conditions. One study found that people with rheumatoid arthritis using tocilizumab did not have a higher cancer risk compared to the general population, suggesting it does not increase cancer risk for these patients.

However, tocilizumab can raise the risk of serious infections, potentially leading to hospitalization or even death. This is crucial for anyone considering joining a clinical trial with this treatment.

Tocilizumab production maintains low levels of impurities, well below harmful limits.

Although the trial is in an early phase, with safety still under close monitoring, these findings offer some insight into the drug's safety. Participants should discuss these points with their healthcare provider to weigh personal risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tocilizumab is unique because it offers a new approach for treating advanced cancer by targeting the immune system's inflammatory response. Unlike traditional chemotherapy or radiation, which directly attack cancer cells, Tocilizumab is an antibody that blocks interleukin-6 (IL-6), a protein involved in inflammation that can promote cancer growth. This treatment is administered intracavitarily, meaning it's delivered directly into the body cavity where the cancer is present, potentially increasing its effectiveness and minimizing systemic side effects. Researchers are excited about its potential to manage cancer's inflammatory environment, offering a novel way to slow disease progression.

What evidence suggests that tocilizumab might be an effective treatment for advanced cancer?

Research has shown that tocilizumab, a drug that blocks a protein involved in inflammation, effectively treats conditions like rheumatoid arthritis. This makes it a promising option for cancer-related issues, as some cancers use inflammation to grow. In past studies, tocilizumab managed severe inflammation caused by certain cancer treatments. Early results from studies using tocilizumab inside body cavities suggest it is safe and may help reduce fluid buildup in conditions like fluid around the lungs and fluid in the abdomen. In this trial, participants will receive incremental weekly intra-cavitary doses of tocilizumab, supporting its potential effectiveness in treating fluid-related cancer symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Patrick Wagner, MD

Principal Investigator

Director of Complex General Surgical Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36271617/

Evaluation of the Tocilizumab therapy in human cancers This review summarized the role of the IL-6/IL-6R axis in inflammation-based cancers and discussed the effectiveness and challenges of treating cancer with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01951170

An Open-Label Study of RoActemra/Actemra (Tocilizumab) ... This open-label, single-arm study will evaluate the efficacy and safety of tocilizumab in patients with active moderate to severe rheumatoid arthritis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6156173/

Tocilizumab for Treatment of Chimeric Antigen Receptor T ... This article summarizes key review findings that supported the approval of tocilizumab for treatment of severe or life‐threatening CAR T cell‐induced cytokine ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950247024000549

Intra-pleural and intra-peritoneal tocilizumab therapy for ... The RIOT-2 study aims to assess the safety of intra-cavitary tocilizumab therapy, administered via indwelling catheters.

5. actemrahcp.com actemrahcp.com/content/dam/gene/actemrahcp/pdfs/actemra-radiate-and-adacta-brochure.pdf

Clinical review of the RADIATE and ADACTA studies No data are available on the effectiveness of vaccination in patients receiving ACTEMRA. ... evidence from the available data that ACTEMRA treatment results ...

6. actemrahcp.com actemrahcp.com/ssc-ild/safety-data.html

Important Safety Information for SSc-ILD HCPs Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40189190/

Risk of cancer in patients with rheumatoid arthritis under ... Conclusion: We found no additional risk factors of cancer for RA patients under TCZ, beyond those already known in the general population.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1297319X25000594

Risk of cancer in patients with rheumatoid arthritis under ... Our study aimed to estimate the incidence and risk factors of cancer among rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ) and followed for ...

9. ema.europa.eu ema.europa.eu/en/documents/assessment-report/tofidence-epar-public-assessment-report_en.pdf

Tofidence, INN-tocilizumab - EMA Data confirm sufficient clearance of the impurities during the manufacturing process. The levels detected are well below toxicology safety ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39523495

Safety outcomes of tocilizumab and tofacitinib treatment for ... We compared the safety outcomes of tocilizumab and tofacitinib in patients with RA in real-world clinical settings, following the 7 key components of target ...