A Multi-omics Approach to Disclose Progression and Underlying Biology of Head and Neck Adenoid Cystic Carcinoma (MAPPING-ACC)

A Multi-omics Approach to Disclose Progression and Underlying Biology of Head and Neck Adenoid Cystic Carcinoma (MAPPING-ACC)

The goal of this observational study is to better understand why some people with metastatic adenoid cystic carcinoma (ACC) of the head and neck have slow-growing disease while others have faster-growing or more aggressive disease. Researchers want to learn how the biology of the tumor relates to each person's clinical risk group, which is based on a published prediction tool (a nomogram).

The main question the study aims to answer is: Do people in the high-risk and low-risk groups have different biological tumor types (called ACC-I and ACC-II) when their primary tumor is tested?

The study will also look at other important questions, such as:

• Do metastatic tumors show the same biological type as the original tumor?
• Do biological types differ based on where metastases grow or how early or late they appear?
• Are biological types linked to how well systemic treatments work?
• Can blood tests (including DNA fragments or small RNA molecules in the blood) show the same tumor biology and help track how the cancer changes over time?

Participants will:

• Allow researchers to study samples of tumor tissue taken in the past during standard care.
• Give blood samples at study entry and then every 6 months for up to 2 years.
• Continue all medical treatments and follow-up visits as decided by their own care team.
• Receive no study treatment; this study only collects information and samples.

About 114 adults with metastatic ACC of the head and neck will join the study. People with only local or regional recurrence (without metastases) or those whose primary tumor started outside the head and neck cannot take part.

The information gathered may help researchers understand why ACC behaves differently from person to person, identify new biological markers in blood, and support future personalized treatment strategies for people with metastatic ACC.

Study Overview

• Status: Recruiting
• Conditions: Adenoid Cystic Carcinoma of the Salivary Gland; Adenoid Cystic Carcinoma of the Head and Neck
• Intervention / Treatment: Other: Standard of Care (Investigator Choice)

• Study Type: Observational
• Enrollment (Estimated): 114

Contacts and Locations

• Study Contact: Name: Lisa Licitra; Phone Number: +39 02 2390 2810; Email: lisa.licitra@istitutotumori.mi.it
• Study Contact Backup: Name: Stefano Cavalieri; Email: stefano.cavalieri@istitutotumori.mi.it

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Contact: Lisa Licitra; Phone Number: +39 02 2390 2810; Email: lisa.licitra@istitutotumori.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Metastatic adenoid cystic carcinoma of head and neck

Description

Inclusion Criteria:

• Pathologic diagnosis of ACC
• Primary ACC arising from the head and neck
• Unequivocal clinical and/or radiological evidence of metastatic disease
• Patient ability and availability to comply with study protocol procedures.

Exclusion Criteria:

• ACC patients with local and/or regional recurrence without distant metastases
• Primary ACC arising from any non-head and neck region (e.g., breast, lung, skin etc)
• Insufficient data about previous medical history.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biology behind the nomogram-based classes of metastatic H&N ACC by assessing the relationship between the two clinical nomogram-based classes (high- vs. low-risk) and the proteogenomic subtype classification (ACC-I vs. ACC-II) in primary tumors	The frequency of cases with ACC-I and ACC-II (proteogenomic subtype classification assessed in primary tumor specimens) in high- vs. low-risk (clinical nomogram-based) metastatic ACC patients.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess if the proteogenomic subtype described in primary tumors is found in distant metastases	The frequency of cases in which the proteogenomic subtype found in primary tumor is unchanged in distant metastases (i.e., percentage of patients with ACC-I in both primary tumor and distant metastases; percentage of patients with ACC-II in both primary tumor and distant metastases) vs. the frequency of cases in which the proteogenomic subtype found in primary tumor is different from the one found in distant metastases (i.e., percentage of patients with ACC-I in primary tumor and ACC-II in distant metastases; percentage of patients with ACC-II in primary tumor and ACC-I in distant metastases)	24 months
To assess if the proteogenomic subtypes in primary tumors reflect the spatio-temporal tumor biology heterogeneity (primary tumor vs. distant metastases; lung vs. non-lung metastases; early vs. late metastases)	The distribution of proteogenomic subtype found in primary tumor and the one found in patients with lung metastases vs. the frequency of proteogenomic subtype found in primary tumor and the one found in patients without lung disease (i.e., percentage of patients with lung metastasis having an ACC-I or an ACC-II profile in primary tumor; percentage of patients without lung metastasis having an ACC-I or an ACC-II profile in primary tumor)	24 months
To assess if the proteogenomic subtype found in primary tumor is associated to objective response to systemic therapy.	The objective response rate (ORR) to systemic therapies based on the proteogenomic subtypes (i.e., ORR in patients with ACC-I vs. ORR in patients with ACC-II).	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess if circulating epigenomic biomarkers (e.g., ct-miRNA; ctDNA-based DNA methylation) are detectable in metastatic ACC patients	To describe the detection rate (i.e., cases with detectable biomarker vs. undetectable biomarker) of circulating epigenomic biomarkers (e.g., ct-miRNA; ctDNA-based DNA methylation) in metastatic ACC patients	24 months
To assess if the biological profile of tumor specimens can be translated on circulating blood	To describe the association with any circulating biomarker with the proteogenomic subtype (ACC-I vs. ACC-II) of pathologic specimens	24 months
To assess if the biological profile of primary tumor can be translated on circulating blood	To describe the association with any circulating biomarker with the proteogenomic subtype (ACC-I vs. ACC-II) of pathologic specimen of primary tumor	24 months
To assess if the biological profile of distant metastasis can be translated on circulating blood	To describe the association with any circulating biomarker with the proteogenomic subtype (ACC-I vs. ACC-II) of pathologic specimen of distant metastases	24 months
To assess if the several clinical profiles under study have an association with specific circulating biomarkers	To describe the association with any circulating biomarker with the clinical nomogram-based class (high- vs. low-risk)	24 months
To assess if qualitative and/or quantitative changes of circulating biomarkers are predictive of clinical progression in ACC natural history	To describe the qualitative and/or quantitative changes of circulating biomarkers in metastatic ACC undergoing a watchful waiting approach	24 months
To assess if the biological profile of the circulating biomarker is able to improve the prognostic capability of the clinical nomogram.	To describe AUC (Area Under the Curve) of overall survival prediction of the circulating biomarker alone vs. clinical nomogram alone vs. the combination of circulating biomarker and clinical nomogram.	24 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; S. Orsola-Malpighi Hospital, University of Bologna; Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale; Azienda Ospedaliera Brotzu; Istituto Oncologico Veneto I.O.V. - I.R.C.C.S.
• Investigators: Principal Investigator: Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: INT156-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No