Cancer, Metastatic Cancer, Solid Organ Cancer
Conditions
Keywords
Immune-related Adverse Events, Immune Checkpoint Inhibitors, Biomarkers, Autoantibodies
Brief summary
The aim of this study is to assess the effectiveness of a battery of autoantibodies to predict the occurrence of immune-related adverse events (irAEs) in patients with cancer who will be treated with immune checkpoint inhibitors (ICIs) per standard protocol.
Detailed description
Introduction: Treatment with ICIs is leading to a remarkable improvement in the prognosis of several types of cancer. However, the expansion of these drugs in the field of oncology is also causing the emergence of a large diversity of irAEs, whose optimal prevention and management are still to be clarified. Nowadays, there is a growing need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs. Purpose: To assess the effectiveness of a battery of autoantibodies available in a laboratory of autoimmunity to predict the occurrence of irAEs in patients with cancer who will be treated with ICIs per standard protocol. Methods: A multicenter prospective observational cohort study was designed to include a total of 221 patients diagnosed with cancer amenable to treatment with ICIs. During a period of 48 weeks, patients will be controlled in the oncology outpatient clinics of five university hospitals with accredited experience in the management of immunotherapy. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. Considering a proportion of irAEs and losses to follow-up of 25% and 5% respectively, a sample size of 221 patients was calculated to estimate an expected sensitivity of the autoantibody battery of 0.90 with a 95% confidence interval not lower than 0.75. All the participants will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE. Both ordinary and extraordinary samples will be frozen and stored in the biobank of each participating hospital in the form of serum and buffy coat. Once the whole cohort reaches the 24th week (intermediate analysis) and the 48th week (definitive analysis), all the samples will be centralized in the same autoimmunity laboratory for the determination of the autoantibody battery. A predictive model of irAEs will be constructed with the autoantibodies together with other potential risk factors of immune-mediated toxicity.
Interventions
DRUGTreatment with immune checkpoint inhibitors.
Treatment with approved immune checkpoint inhibitors, namely ipilimumab, nivolumab, pembrolizumab, atezolizumab and avelumab, alone or in combination, administered per standard protocol.
DIAGNOSTIC_TESTBlood tests.
Patients will undergo ordinary blood tests obtained at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE.
Sponsors
Hospital de Basurto
Hospital Donostia
Complejo Hospitalario de Navarra
Hospital Galdakao-Usansolo
Hospital Universitario Araba
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Initiation of treatment with a single ICI or a combination of ICIs. 2. Acceptation of an informed consent.
Exclusion criteria
1. Life expectancy lower than 3 months from the initiation of treatment with ICIs. 2. Proven hypersensitivity or previous allergic anaphylactic reaction induced by a specific ICI. 3. Active autoimmune disease with severe involvement. 4. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3. 5. Ongoing immunosuppressive therapy: prednisone at doses \>10 mg/day or equivalent (\>1.5 mg/day of dexamethasone), and/or any dose of azathioprine, methotrexate, mycophenolate, cyclophosphamide, leflunomide, rituximab, anti-tumor necrosis factor drugs (infliximab, etanercept, adalimumab, golimumab), belimumab and abatacept.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of irAEs. | At 48 weeks from the initiation of ICIs. | An irAE was defined as any symptom, sign, syndrome or disease attributable to an immune activation mechanism during an ongoing treatment with an ICI or a combination of ICIs, provided that an infectious cause and/or tumor progression have been ruled out. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| irAE-free survival. | At 24 weeks and at 48 weeks from the initiation of ICIs. | Time in months from the initiation of therapy with ICIs until the occurrence of an irAE or until the date of the last follow-up. |
| Progression-free survival. | At 24 weeks and at 48 weeks from the initiation of ICIs. | Time in months from the initiation of therapy with ICIs until the date of proven tumor progression or until the date of the last follow-up. |
| Overall survival. | At 24 weeks and at 48 weeks from the initiation of ICIs. | Time in months from the initiation of therapy with ICIs until the date of patient's death or until the date of the last follow-up. |
| Incidence of development of autoantibodies. | At 24 weeks and at 48 weeks from the initiation of ICIs. | Positive conversion of the autoantibody battery after the initiation of therapy with ICIs. |
Countries
Spain
Outcome results
None listed