Clinical trial NCT03868046: Autoantibodies in Treatment with Immune Checkpoint Inhibitors (AUTENTIC)
Official title: Prediction of Immune-related Adverse Events Induced by Anti-CTLA4 and Anti-PD1/PDL1 Drugs by Means of a Battery of Autoantibodies. a Multicenter Prospective Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Metastatic Cancer
Solid Organ Cancer
Keywords: Immune-related Adverse Events
Immune Checkpoint Inhibitors
Biomarkers
Autoantibodies
Lead sponsor: Hospital Universitario Araba
Sponsor class: OTHER
Collaborators: name: Hospital de Basurto
name: Hospital Donostia
name: Complejo Hospitalario de Navarra
name: Hospital Galdakao-Usansolo
First posted: 2019-03-08
Enrollment: 242
Sex: ALL
Minimum age (years): 16
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients diagnosed with cancer amenable to treatment with ICIs will be considered eligible. Potential candidates will be identified and consecutively included in the oncology outpatient clinics of five university hospitals in Spain.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of irAEs.
timeFrame: At 48 weeks from the initiation of ICIs.
Secondary outcomes:
measure: irAE-free survival.
timeFrame: At 24 weeks and at 48 weeks from the initiation of ICIs.
measure: Progression-free survival.
timeFrame: At 24 weeks and at 48 weeks from the initiation of ICIs.
measure: Overall survival.
timeFrame: At 24 weeks and at 48 weeks from the initiation of ICIs.
measure: Incidence of development of autoantibodies.
timeFrame: At 24 weeks and at 48 weeks from the initiation of ICIs.
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital Universitario Araba
state: Álava
Study officials:
affiliation: Hospital Universitario Araba
name: Iñigo Les Bujanda, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: