Clinical trial NCT05904327: Circulating Biomarkers in Oropharyngeal Cancers
Official title: The Use of Circulating Biomarkers in Oropharyngeal Cancer and Unknown Primary of Head and Neck - a Prospective Multicenter Study for Treatment Evaluation and Surveillance
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Oropharynx Squamous Cell Carcinoma
Oropharynx Cancer
Tonsillar Cancer
Base of the Tongue Carcinoma
Keywords: circulating tumor DNA
HPV
human papilloma virus
Lead sponsor: Region Örebro County
Sponsor class: OTHER
Collaborators: name: Region Stockholm
name: Region Västmanland
name: Dalarna County Council, Sweden
name: Sormland County Council, Sweden
name: Värmland County Council, Sweden
First posted: 2023-06-15
Enrollment: 130
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study participants are recruited from multidisciplinary conferences of head and neck cancer at Örebro University hospital - Region Örebro County, Västmanland's hospital - Region Västmanland and Karolinska University hospital - Region Stockholm. Örebro University hospital is a tertiary referral hospital of three regions in central Sweden (Region Värmland, Region Sörmland and Region Dalarna) and therefore patients from these regions will also be included in this study. All patients with OPSCC at any of the study centers will be asked to participate in CIRCOS. All study participants will sign an informed written consent upon inclusion

Brief summary: The goal of this observational longitudinal study is to learn about circulating tumor Human Papilloma Virus-DNA (ctHPV-DNA) as a biomarker for HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck. The main questions it aims to answer are:

* Can ctHPV-DNA be used for treatment evaluation in HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck?
* Can circulating HPV-DNA be used as a biomarker for recurrent disease during surveillance?

Participants will be asked to leave plasma samples at diagnose, at the end of treatment and at every clinical follow-up.

The patients are there own controls.

Detailed description: In the multicenter study of CIRCOS, Circulating biomarkers in oropharyngeal cancer, patients with oropharyngeal cancer or cancer of unknown primary of the head and neck are consecutively included. Plasma samples are collected at diagnosis, at the end of treatment and during surveillance after treatment.

At diagnose participants will fill in informed consent and a form regarding known risk factors for cancer. Tissue from the tumor will be analyzed for HPV genotype with a multiplex q-PCR. Information about p16 will be collected from medical records.

ctHPV-DNA are short DNA fragments that leaks into the blood stream from tumor cells during apoptosis and necrosis. In the study, ctHPV-DNA will be extracted from blood plasma. Levels of ctHPV-DNA (copies/mL) will be measured using digital droplet PCR (ddPCR) with genotype specific assays (based on the result of q-PCR at diagnose) used in singleplex (SAGA diagnostics). A negative sample after treatment will be defined as a good molecular response for evaluation after treatment. Two consecutive, positive samples during surveillance will be defined as molecular recurrence. If a molecular recurrence is seen patients will be contacted and offered an extra clinical control at an Ear nose and throat department.

If a patient is HPV negative in tissue, the tissue will be analyzed with whole genome sequencing. If a mutation is found, a personalized ddPCR-kit will be used for plasma.

All patients will be followed for five years.

Eligibility criteria: Inclusion Criteria:

* Oropharyngeal cancer
* Cancer of unknown primary in the head and neck

Exclusion Criteria:

* Previous treatment of cancer in the oropharynx.
* Previous treatment of unknown primary tumor.
* Remote metastases
* Patients unwilling or unable to comply with the study protocol and follow-up schedule

Primary outcomes:
measure: The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
timeFrame: 5 year follow-up
Secondary outcomes:
measure: The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient.
timeFrame: 3 months follow-up
measure: A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test.
timeFrame: 3 months follow-up
Other outcomes:
Locations:
city: Orebro
country: Sweden
facility: Anna Oldaeus Almerén
Study officials:
affiliation: Örebro University, Sweden
name: Gisela Helenius
role: STUDY_DIRECTOR
References: