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CompletedNCT03868046AUTENTICUpdated Apr 1, 2025

Autoantibodies in Treatment with Immune Checkpoint Inhibitors (AUTENTIC)

An observational study in Cancer, Metastatic Cancer and Solid Organ Cancer, sponsored by Hospital Universitario Araba. Completed at 1 site in Spain. Open to participants aged 16 Years to 99 Years. Per ClinicalTrials.gov, last updated 2025-04-01.

Sponsored by Hospital Universitario Araba · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
242
Ages
16 Years to 99 Years
Sex
All
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Study 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.

Read the 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.

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Conditions studied

  • Cancer
  • Metastatic Cancer
  • Solid Organ Cancer

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Keywords

  • Immune-related Adverse Events
  • Immune Checkpoint Inhibitors
  • Biomarkers
  • Autoantibodies
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Who can participate

Ages eligible
16 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No
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.

Inclusion criteria

  1. Initiation of treatment with a single ICI or a combination of ICIs.
  2. Acceptation of an informed consent.

Exclusion criteria

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.
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
242 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Patients treated with ICIs.

    All enrolled patients must have been diagnosed with a cancer potentially treatable with ipilimumab, nivolumab, pembrolizumab, atezolizumab or avelumab, alone or in combination, per standard protocol.

    Drug: Treatment with immune checkpoint inhibitors. · Diagnostic Test: Blood tests.

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.

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What researchers measure

Primary outcomes

  1. Incidence of irAEs.

    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.

    Time frame: At 48 weeks from the initiation of ICIs.

Secondary outcomes

  1. irAE-free survival.

    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.

    Time frame: At 24 weeks and at 48 weeks from the initiation of ICIs.

  2. Progression-free survival.

    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.

    Time frame: At 24 weeks and at 48 weeks from the initiation of ICIs.

  3. Overall survival.

    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.

    Time frame: At 24 weeks and at 48 weeks from the initiation of ICIs.

  4. Incidence of development of autoantibodies.

    Positive conversion of the autoantibody battery after the initiation of therapy with ICIs.

    Time frame: At 24 weeks and at 48 weeks from the initiation of ICIs.

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Study locations

1 site
  • Hospital Universitario Araba
    Vitoria, Álava 01009, Spain
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References and documents

Individual participant data

Plan to share: Yes — All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

No publications or documents are linked to this record.

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Registry details

Key details

Study ID
NCT03868046
Lead sponsor
Hospital Universitario Araba
Collaborators
Hospital de Basurto, Hospital Donostia, Complejo Hospitalario de Navarra, Hospital Galdakao-Usansolo
Responsible party
Iñigo Les Bujanda (Principal Investigator, Hospital Universitario Araba) — Principal investigator
First posted
Mar 8, 2019
Start date
Aug 25, 2019
Primary completion
Oct 31, 2023
Completion
Dec 31, 2023
Last update
Apr 1, 2025

Study contacts

Iñigo Les Bujanda, MD PhD
principal investigator · Hospital Universitario Araba

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.

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