Immune therapy related adverse events (arthritis and colitis) in patients with solid tumors MedDRA version: 20.0 Level: PT Classification code 10009887 Term: Colitis System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 20.0 Level: PT Classification code 10003246 Term: Arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Herlev and Gentofte Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent o Subjects must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care o Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study • Patients with solid tumors treated with PD-1, PD-L1 and /or CTLA-4 inhibitors • Diarrhea and/or colitis CTCAE grade ? 1 and/or arthritis CTCAE grade ? 1 induced by PD-1, PD-L1 and /or CTLA-4 inhibitors • Age 18 years and older • ECOG/WHO Performance Status (PS) 0-1, PS of 2 due to ongoing irAEs is allowed • White blood cell count (WBC) = 2 x 10?/L and/or absolute neutrophil count (ANC) = 1.0 x 10?/L • Platelet count = 50 x 10?/L • Serum bilirubin = 1.5 x upper limit of normal (ULN) • ASAT/ALAT = 5 x ULN Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • History of allergy to study drug component • Patients should be excluded if they have a condition and/or other irAEs requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration • Females of childbearing potential or males of reproductive potential who are not willing to use an effective method of contraception, such as oral, injected, or implanted hormonal methods of contraception, intrauterine device or intrauterine system, condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, suppository, male sterilization, or true abstinence throughout study and for a minimum of 3 months after study drug therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical benefit of IL-6 inhibition by tocilizumab on diarrhea and/or colitis and/or arthritis induced by checkpoint inhibitors in patients with solid tumors within 8 weeks of treatment start. ;Secondary Objective: Safety, tolerability and feasibility of tocilizumab. Evaluate the clinical benefit of IL-6 inhibition by tocilizumab on diarrhea and/or colitis and/or arthritis induced by checkpoint inhibitors in patients with solid tumors without corticosteroids within 8 weeks of treatment start Evaluate prolonged sustained glucocorticoid-free remission at week 24 Exploratory: Investigate changes of IL-6, IL-8, IL-17, CD4+ and CD 8+ T cells, Tregs, Th17 T cells, ANA RF, anti-CCP, CRP, WBC, ANC, CD163 and 90 proteins associated with inflammation and cancer using the Immuno-Oncology protein panel from Olink Investigate imaging changes and inflammation changes in colon if biopsies are available Quantitatively determine the composition of the microflora and their gene and protein expression levels in patients with solid tumors being treated with checkpoint inhibitors and to compare the changes in species composition and in the metabolic activities with response to tocilizumab and immunotherapy;Primary end point(s): • Rate of at least one grade improvement after tocilizumab using the NCI CTCAE v5.0 within 8 weeks of treatment start ;Timepoint(s) of evaluation of this end point: 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1:Safety (Data on safety parameters). 2: Rate of at least one grade improvement without prednisolone using the NCI CTCAE v5.0. within 8 weeks of treatment start 3: Rate of sustained glucocorticoid-free remission at week 24 Exploratory: 4:Changes of IL-6, IL-8, IL-17, CD4+ and CD 8+ T cells, Tregs, Th17 T cells, ANA RF, anti-CCP, CRP, WBC, ANC, CD163 and 90 proteins associated with inflammation and cancer using the Immuno-Oncology protein panel from Olink, fecal composition of the microflora, imaging changes and inflammation changes in colon if biopsies are available. ;Timepoint(s) of evaluation of this end point: 1: Complete treatment period 2: 8 weeks 3: 24 weeks 4: Complete treatment period | — |
Countries
Denmark
Contacts
Public ContactCoordinating Investigator
Herlev and Gentofte Hospital
Outcome results
None listed