CIRCOS: Circulating Biomarkers in Oropharyngeal Cancers

Sponsor

Region Örebro County (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05904327

Collaborator

Region Stockholm (Other), Region Västmanland (Other), Dalarna County Council, Sweden (Other), Sormland County Council, Sweden (Other), Värmland County Council, Sweden (Other)

130

Enrollment

Location

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Oropharynx Squamous Cell Carcinoma Oropharynx Cancer Tonsillar Cancer Base of the Tongue Carcinoma

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.

Study Design

Study Type:

Observational

Actual Enrollment :

130 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Mar 31, 2028

Anticipated Study Completion Date :

Mar 31, 2028

Outcome Measures

Primary Outcome Measures

The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV [5 year follow-up]
ctHPV-DNA will be evaluated by ddPCR. Two consecutive positive values will be defined as a molecular recurrance. The accuracy of the test will be presented with negative predictive value (NPV) and positive predictive value (PPV) at one, two (interim analysis) and at five year follow-up

Secondary Outcome Measures

The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient. [3 months follow-up]
Correlation of ctHPV-DNA and radiologic tumor burden at diagnosis and post treatment. ctHPV-DNA will be evaluated by ddPCR (copies/mL) at diagnose and at the end of treatment. The levels of ctHPV-DNA will be used as a measure of molecular tumor burden. The molecular tumor burden will be compared with the radiologic tumor burden, measured in diameter and volume in the diagnostic and evaluation computed tomography. The correlation will be calculated using Kendall rank correlation coefficient
A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test. [3 months follow-up]
The kinetics in ctHPV-DNA and will be compared to radiological confirmed treatment response in order to test ctHPV-DNA as a biomarker for treatment response. Radiological response will be evaluated according to the RECIST-criteria. Kinetics of ctHPV-DNA will be described as percentage change between pre- and post-treatment levels of ctHPV-DNA.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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