E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune therapy related adverse events (arthritis and colitis) in patients with solid tumors |
|
E.1.1.1 | Medical condition in easily understood language |
Side effects (diarrhea and arthritis) due to immunotherapy given to patients with cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009887 |
E.1.2 | Term | Colitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003246 |
E.1.2 | Term | Arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
|
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 10⁹/L and/or absolute neutrophil count (ANC) ≥ 1.0 x 10⁹/L
• Platelet count ≥ 50 x 10⁹/L
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• ASAT/ALAT ≤ 5 x ULN
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | 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.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Complete treatment period
2: 8 weeks
3: 24 weeks
4: Complete treatment period |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |