Circulating Biomarkers in Oropharyngeal Cancers (CIRCOS)

June 13, 2023 updated by: Region Örebro County

The Use of Circulating Biomarkers in Oropharyngeal Cancer and Unknown Primary of Head and Neck - a Prospective Multicenter Study for Treatment Evaluation and Surveillance

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.

Study Overview

Status

Active, not recruiting

Conditions

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 Type

Observational

Enrollment (Actual)

130

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Orebro, Sweden
        • Anna Oldaeus Almerén

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
Time Frame: 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
5 year follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient.
Time Frame: 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
3 months follow-up
A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test.
Time Frame: 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.
3 months follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Örebro County

Collaborators

Värmland County Council, Sweden
Region Stockholm
Dalarna County Council, Sweden
Region Västmanland
Sormland County Council, Sweden

Investigators

  • Study Director: Gisela Helenius, Örebro University, Sweden

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2020

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

April 17, 2023

First Submitted That Met QC Criteria

June 13, 2023

First Posted (Actual)

June 15, 2023

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 278627

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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