CITAR study: Checkpoint Inhibitor Treatment of ARthritis

CITAR - Comparison of the efficacy and safety of early use of IL-6R blockade by tocilizumab in combination with short-term glucocorticoids versus glucocorticoids alone for the treatment of cancer immunotherapy-induced arthritis with checkpoint inhibitors: a randomised, open-label, multicentre, proof-of-concept, superiority, controlled clinical trial

EUCT number: 2022-501130-33-00

Find out more about the CITAR clinical trial:
https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2022-501130-33-00

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Sponsor AP-HP - Project code: APHP 240143
Coordinating Investigator: Dr Samuel BITOUN - Rheumatology Department CHU Bicêtre
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01.45.21.72.87

Contact Karolinska Institutet (KI) Email:Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser.

Study methodology

Phase II trial
Randomised
Controlled
Open-label
Multicentre
Rheumatology units

Study population and number of subjects

Patients treated with immune checkpoint inhibitors (ICI) for cancer who develop ICI-induced inflammatory arthritis.
112 patients (56 in each group)
Including 30 in France

Primary objective

Evaluation of the effect of early use of tocilizumab in combination with glucocorticoids (15 days) (arm B) VS glucocorticoids alone (arm A) on CDAI at week 16.

Study treatment

Arm A : Perdnisolone

001

Arm B : Tocilizumab + Prednisolone reduction

002

Inclusion Criteria

Patients with histologically (or cytologically) confirmed cancer who develop arthritis (diagnosed by a rheumatologist) secondary to treatment with immune checkpoint inhibitors*.

*Patients may be on monotherapy with ICIs or on combination therapy with two ICIs (e.g. ipilimumab and nivolumab). Patients may be on ICI in combination with chemotherapy.

At least 2 joints involved (clinically defined) AND CDAI > 10
Performance status of (ECOG/OMS) 0-1, a performance status of 2 due to ongoing irAEs is allowed
Patients already taking glucocorticoids, at any dose, for the treatment of arthritis may be included, if the duration of glucocorticoid treatment does not exceed 1 week.
Women of childbearing potential must have a negative pregnancy test (blood or urine) at inclusion.

Women must have been post-menopausal for at least 1 year or be willing and able to use highly effective contraception during treatment and up to 3 months after the last dose of study drug

Non-inclusion criteria

Mild arthritis requiring no treatment other than NSAIDs or analgesics
Presence of a life-threatening or organ-threatening treatment-related adverse event (TRAE) requiring high doses of glucocorticoids
Current glucocorticoid treatment for other indications that cannot be stopped
History of inflammatory rheumatic disease prior to cancer diagnosis
Current participation or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of treatment
Diagnosis of immunodeficiency or current systemic immunosuppressive therapy, other than steroids, prior to the first dose of study treatment
Treatment with a non-biologic immunosuppressive or immune modulating drug
Treatment with other biological immune-modulating agents (other than ICIs) within 4 weeks prior to the start of treatment
Vaccination with a live vaccine within 4 weeks prior to the first dose of study drug or anticipated need for live vaccination during the study, including at least 30 days after the last dose of study drug.
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 biological composition to tocilizumab.
History of hypersensitivity to prednisolone or any of its excipients.
History of HIV or other immunodeficiencies
History or current evidence of any condition, therapy, or laboratory abnormality that could bias the trial results, interfere with the subject's participation throughout the trial, or that would not be in the best interest of the subject to participate, in the opinion of the treating investigator.
History of psychiatric or substance abuse disorders that would interfere with cooperation with trial requirements
History of chronic viral hepatitis, alcoholic or metabolic liver disease
Central nervous system (CNS) metastases
History or current positive purified protein-derived tuberculin (PPD) test
Transplanted organs
Active infection
Pregnancy or breast-feeding
Pre-existing central nervous system demyelinating disorders or seizure disorders
History of diverticulitis, diverticulosis requiring antibiotic treatment, or other symptomatic gastrointestinal (GI) conditions likely to favour perforations
Adequate organ and bone marrow function
Aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT) (SGPT) ≤2 × institutionalupper normal limit
Creatinine clearance Creatinine clearance ≥30 mL/min

Study progress

002

Arm A/arm B follow-up visits

Examinations every 4 weeks:

002

Information collected

ICI treatment : continuation, cessation, dose reduction, pause
Cancer progression: oncology assessment and CT scan controls
Functional status: ECOG/WHO PS
Concomitant medications
Adherence to treatment

PROs (Patient-Reported Outcomes)

VAS pain
VAS general health
VAS fatigue
HAQ
EQ5D

Physical examination

Blood pressure, heart rate
Assessment of tenderness and swelling in 66/68 joints
Blood tests
Urine pregnancy test

Pharmacy circuit

002

Other contacts :

DRCI Project Manager: Charline MENANTEAU Clinical Research and Innovation Department (DRCI)
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01.40.27.41.78

DRCI-URC Project Manager: Ikrame RAMDHANI
URC Paris Sud, Hôpital Bicêtre E-mail: Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser.
01. 45.21.21.80

Clinical Research Associate: Chanez HADDADOU
URC Paris Sud, Hôpital Bicêtre E-mail: Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser.
01.45.21.63.23

CITAR Referent at the Institut Gustave Roussy:
Dr Clea BARDON Email: Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser.
01.45.22 25 22