Role of Liquid Biopsies in HPV-associated Cancer Treatment Monitoring

March 7, 2023 updated by: The Institute of Molecular and Translational Medicine, Czech Republic

Liquid Biopsies - a Possible Tool for Treatment Monitoring and Early Recurrence Detection in HPV-associated Diseases

This trial will evaluate the possible benefits and the performance of liquid biopsies in HPV-associated cancer treatment monitoring. This study aims to find a combination of an adequately sensitive and specific sampling method and biomarkers for early risk stratification of disease recurrence.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although the cancers associated with human papillomavirus (HPV) infection are currently almost entirely preventable, a significant part of the Czech population suffers from these diseases. The most common HPV-associated cancers are cervical cancer (CC) and oropharyngeal cancer (OPC). In these, the severe problem is successful monitoring of the treatment effectiveness and early disease recurrence detection. It is, therefore, necessary to find a non-invasive method that could specifically and timely identify patients at risk of recurrence and thus enable patients with quality and less burdensome medical care. The use of liquid biopsies (LB), which the study focuses on, looks most promising.

This study is divided into two arms, with each arm including both prospective and retrospective parts. Into prospective parts will be enrolled only newly diagnosed CC/HSIL (high-grade cervical intraepithelial lesions) or OPC patients. In contrast, the retrospective part will enroll patients in post-treatment follow-up. In both study arms, fresh tumor tissues will be sampled from patients in prospective parts before treatment, and archived Formalin Fixed Paraffin Embedded (FFPE) tissue samples will be obtained from patients of retrospective parts.

Regarding the liquid biopsies, pre & post-treatment sampling of LB will be performed. Subsequently, regular sample acquisition will be performed during follow-up according to the standard medical practice in both prospective and retrospective parts. Oropharyngeal swabs, gargle lavage,exhaled breath condensate (EBC), and blood samples will be collected from OPC patients. Blood collection and self-sampling of cervicovaginal swabs will be performed in patients with CC/HSIL. All samples, excluding blood samples, will be tested for the presence of the most prevalent high-risk and low-risk HPV genotypes. The circulating tumor (ct) HPV DNA will be monitored in blood samples. Additionally, the mutation profile of the primary tumors will be examined in fresh and FFPE samples.

The dynamics of HPV DNA will be monitored throughout all follow-up samples and correlated with the obtained clinical data. A created panel of frequently altered genes will be used for alterations monitoring in liquid biopsies. In the final analysis of laboratory and clinical results, we assume a finding of a clinically usable algorithm that could predict the risk of disease recurrence for a particular patient.

Study Type

Interventional

Enrollment (Anticipated)

480

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Czechia
      • Olomouc, Czechia, 77900
        • Recruiting
        • University Hospital Olomouc
        • Contact:
        • Contact:
        • Principal Investigator:
          • Radovan Pilka, prof. MD,PhD
        • Principal Investigator:
          • Richard Salzman, MD, PhD.

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

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Women diagnosed with CC/HSIL. Men and women diagnosed with OPC. Patients must agree with study enrollment and must sign study informed consent.

Exclusion Criteria:

No exclusion criteria are set.

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

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A - Oropharyngeal cancer patients
In total, approx. 200 OPC cancer patients will be enrolled in the study Arm A, with both prospective and retrospective parts enrolling 100 OPC patients. The Arm A will enroll patients from the Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Olomouc. Pre-treatment primary samples of fresh or FFPE tissue samples will be collected. Liquid biopsies (gargle lavage, oropharyngeal smear, breath condensate, and blood sample) will be collected. Obtained samples will be tested by CE-IVD (device complies with European in vitro diagnostic Directive) marked HPV diagnostic test. A laboratory developed digital droplet PCR assay will be used for ct HPV DNA detection. Sampling will be performed at pre & post treatment check-ups, and every 3 months for 3 years and every 6 months for 2 years.
Diagnostic test: Arm A - Diagnostic test: HPV detection in liquid biopsies
Patients will be asked to perform self-collection of gargle lavage samples. Oropharyngeal swabs, breath condensate, and blood samples will be taken by trained clinicians.
Active Comparator: Arm B - Cervical cancer patients
Into the study Arm B will be enrolled 80 patients with CC and 120 patients with HSIL, and 80 patients will be enrolled into the retrospective part. The Arm B will enroll patients from the Department of Gynecology and Obstetrics, University Hospital Olomouc. Pre-treatment primary samples of fresh or FFPE tissue samples will be collected. Liquid biopsies (cervicovaginal swab and blood sample) will be collected. Obtained samples will be tested by CE-IVD marked HPV diagnostic test. A laboratory developed digital droplet PCR assay will be used for ct HPV DNA detection. Sampling will be performed at pre & post treatment check-ups, and every 3 months for 2 years and every 6 months for 3 years.
Diagnostic test: Arm B - Diagnostic test: HPV detection in liquid biopsies
Patients will be asked to perform cervicovaginal self-sampling using Evalyn Brush. Blood samples will be taken by trained clinicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dynamics of HPV infection in cervical cancer patients during 4-year follow-up.
Time Frame: 4 years
HPV-status in liquid biopsies collected during pre-treatment, post-treatment and follow-up check-ups.
4 years
Dynamics of HPV infection in oropharyngeal cancer patients during 4-year follow-up.
Time Frame: 4 years
HPV-status in liquid biopsies collected during pre-treatment, post-treatment and follow-up check-ups.
4 years
Dynamics of circulating tumor (ct) HPV DNA in oropharyngeal cancer patients.
Time Frame: 4 years
Correlation of plasmatic ct HPV DNA level with cancer patient´s prognosis.
4 years
Dynamics of circulating tumor (ct) HPV DNA in cervical cancer patients
Time Frame: 4 years
Correlation of plasmatic ct HPV DNA level with patient´s prognosis
4 years
Analysis of the mutational landscape of oropharyngeal cancer cases.
Time Frame: 4 years
Correlation of tumor mutational burden (TMB) with cancer patient´s prognosis.
4 years
Analysis of the mutational landscape of cervical cancer cases.
Time Frame: 4 years
Correlation of tumor mutational burden (TMB) with cancer patient´s prognosis.
4 years

Collaborators and Investigators

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

Sponsor

The Institute of Molecular and Translational Medicine, Czech Republic

Collaborators

University Hospital Olomouc
Cancer Research Czech Republic

Investigators

  • Study Director: Marian Hajduch, MD., PhD., IMTM, Palacky University in Olomouc, Faculty of Medicine and Dentistry

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)

June 1, 2022

Primary Completion (Anticipated)

May 31, 2026

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

January 24, 2023

First Submitted That Met QC Criteria

March 7, 2023

First Posted (Actual)

March 17, 2023

Study Record Updates

Last Update Posted (Actual)

March 17, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NU-23-03-00255

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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