CITAR - Comparison of the efficacy and safety of early use of IL-6R blockade with tocilizumab in combination with short-term glucocorticoids versus glucocorticoids alone for the treatment of arthritis induced by cancer immunotherapy by check point inhibitors: a randomized, open, multicentre, proof of concept, superiority, controlled clinical trial
- Conditions
- Patients with histologically (or via cytology) confirmed cancer that develop arthritis secondary to treatment with immune checkpoint inhibitors.MedDRA version: 21.1Level: PTClassification code: 10067961Term: Eastern Cooperative Oncology Group performance status Class: 100000004848Therapeutic area: Phenomena and Processes [G] - Immune System Phenomena [G13]Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- CTIS2022-501130-33-00
- Lead Sponsor
- Karolinska University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 30
The subject is willing and able to give informed consent to participate in the trial, = 18 years of age on day of signing informed consent, Patients with histologically (or via cytology) confirmed cancer who develop arthritis (as diagnosed by a rheumatologist) secondary to treatment with immune checkpoint inhibitors. *Patients can be on or have received monotherapy with ICI or combination therapy with two ICIs (e.g. ipilimumab and nivolumab). Patients can be on or have received ICI in combination with chemotherapy. All the different ICI that are currently approved by EMA and in clinical use will be allowed (ipilimumab, nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, relatlimab). Additional ICI under investigation can also be authorized, as long as the patient is not participating already in a clinical trial., At least 2 joints involved (clinically defined) AND CDAI >10., The Eastern Cooperative Oncology Group/World Health Organization Performance Status (ECOG/WHO PS) 0-1, PS of 2 due to ongoing irAEs is allowed, Patients already on glucocorticoids regardless of dose for the treatment of the arthritis can be included, if the duration of the glucocorticoid treatment is maximum 1 week, Women of child-bearing potential must have a negative pregnancy test (serum or blood) at inclusion., Female subjects must be 1 year post-menopausal or be willing and able to use highly effective contraception during the treatment and up to 3 months after the last dose of IMP. Oral, injected or implanted hormonal contraceptive, intrauterine device, intrauterine hormone-releasing system, surgical sterilization, transdermal delivery, congenital sterility, vasectomised partner or sexual abstinence are considered acceptable forms of birth control.
Mild arthritis that does not require treatment other than NSAID (non-steroidal anti-inflammatory drugs) or analgetics, Pregnancy or Breastfeeding, Preexisting central nervous system demyelinating or seizure disorders, Concomitant life or organ threatening irAE which requires high doses of glucocorticoids (e.g. pneumonitis, myocarditis etc). This is assessed and defined clinically at screening by the treating oncologists and rheumatologists., History of diverticulitis, diverticulosis requiring antibiotic treatment, or other symptomatic lower gastrointestinal (GI) conditions that might predispose to perforations, Have adequate organ and marrow function as defined below: Absolute Neutrophil Count =1,000/microliters Platelets =100,000 Hemoglobin = 7.0g/dL (without transfusion in past 2 weeks). Note: Patients with cytopenias (e.g immune thrombocytopenia, autoimmune hemolytic anemia) clinically consistent with irAE will be eligible at the discretion of principal investigator. Aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT)(SGPT) =2 × institutional upper limit of normal Creatinine clearance of = 30 mL/min. Creatinine clearance (CrCl) should be calculated at screening using the Cockcroft-Gault formula, Current treatment with glucocorticoids for other indications (i.e. cerebral metastasis) that is not possible to discontinue, Patients with a history of inflammatory rheumatic disease prior to cancer diagnosis, Current participation in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment, Diagnosis of immunodeficiency or ongoing systemic immunosuppressive therapy other than steroids prior to the first dose of trial treatment, Treatment with a non-biologic immunosuppressive or immune-modulating drug (e.g. methotrexate, azathioprine, mycophenolate, cyclosporine, hydroxychloroquine, penicillamine) within 4 weeks prior to treatment, History of human immunodeficiency virus (HIV) infection or other immunodeficiency, Treatment with other immune-modulating biologic agents (other than the ICI) within 4 weeks prior to treatment initiation, History of anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or any component of tocilizumab. History of allergic reactions attributed to compounds of similar chemical or biologic composition to tocilizumab, Vaccination with a live vaccine within 4 weeks prior to the first dose of study drug or expected need of live vaccination during study, including at least 30 days after the last dose of study drug., History of hypersensitivity to Prednisolone or to any of the excipients., History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator., Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial, History of chronic viral hepatitis, alcoholic or metabolic liver disease. Carriers of hepatitis B and patients with a history of hepatitis B infection or positive serology are excluded except in situations where the potential benefit is determined to justify the risk of possible hepatitis B reactivation, which can be fatal. Patients with positive serology should have viral DNA level
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method