Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)

Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03868046
• Other study ID #: PI2018106 (EPA-SP)
• Status: Recruiting
• Start date: August 25, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: Hospital Universitario Araba
• Contact: Iñigo Les Bujanda, MD PhD
• Phone: 0034636346833
• Email: ilesbujanda[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 221
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Metastatic Cancer
• Neoplasm Metastasis
• Solid Organ Cancer

Intervention

Drug:
• Treatment 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 Test:
• Blood 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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Araba	Vitoria	Álava

Sponsors (5)

Lead Sponsor	Collaborator
Hospital Universitario Araba	Complejo Hospitalario de Navarra, Hospital de Basurto, Hospital Donostia, Hospital Galdakao-Usansolo

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 48 weeks from the initiation of ICIs.
Secondary	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.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Secondary	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.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Secondary	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.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Secondary	Incidence of development of autoantibodies.	Positive conversion of the autoantibody battery after the initiation of therapy with ICIs.	At 24 weeks and at 48 weeks from the initiation of ICIs.