Search
Close this search box.

SURVEILLE-HPV: Evaluation of HPV16 Circulating DNA as Biomarker to Detect the Recurrence, in Order to Improve Post Therapeutic Surveillance of HPV16-driven Oropharyngeal Cancers

Studies

Study First Submitted Date 2022-10-11
Study First Posted Date 2022-10-17
Last Update Posted Date 2023-04-05
Start Month Year March 1, 2024
Primary Completion Month Year March 1, 2028
Verification Month Year April 2023
Verification Date 2023-04-30
Last Update Posted Date 2023-04-05

Conditions

Sequence: 52428341
Name Oropharynx Squamous Cell Carcinoma
Downcase Name oropharynx squamous cell carcinoma

Id Information

Sequence: 40341452
Id Source org_study_id
Id Value UC-HNG-2209

Design Groups

Sequence: 55878591 Sequence: 55878592
Group Type No Intervention Group Type Experimental
Title Standard follow-up monitoring (16 visits over 5 years) Title Lightened follow-up visits frequency (9 visits over 5 years), with HPV16 Ct-DNA dosing
Description Patients enrolled in the control arm will be monitored according to SFORL guidelines. Physical Examination (PE) will be carried out: – every 2 months the 1st year, every 3 months the 2nd year, every 4 months the 3rd year, every 6 months at 4 and 5 years. Annual chest CT scan will be performed for current smokers & for those who have quit smoking less than 15 years ago. Description Physical Examinations (with HPV16 Ct-DNA dosing) planned at Months 4,8,12,18,24,30,36,48,60 post treatment. Annual chest CT scan will be performed for current smokers & for those who have quit smoking less than 15 years ago. Any patient with a normal PE but positive HPV16 ct-DNA test during follow-up period will require a confirmation test ~1-2 months later. If HPV16 ct-DNA positivity is confirmed, an H&N MRI /PET-CT will be performed. Then: If MRI and PET-CT are negative, the patient will be examined every 2 months (PE and HPV16 Ct-DNA dosing) and MRI/PET-CT will be repeated every 4-6 months, until HPV16 Ct-DNA becomes undetectable. If MRI and/or PET-CT is positive, the patient will get a biopsy to confirm disease recurrence. Once confirmed, the patient will have the necessary care, as per local practices, but will continue to be followed up within this study up to 5 years after treatment.

Interventions

Sequence: 52737677
Intervention Type Biological
Name HPV16 Ct-DNA dosing
Description Droplet based digital PCR (ddPCR) technology is a novel method for performing digital PCR. A sample is fractionated into 20,000 droplets, PCR amplification of the template molecules occurs in each individual droplet. ddPCR allows to generate quantitative and accurate data without standard curves and also present higher sensitivity compared to conventional quantitative PCR (qPCR). Indeed, this method is based on the realization of millions of single-molecule PCRs in parallel in independent compartment (here droplets of an emulsion) and consequently avoids the bias seen in conventional PCR. ddPCR offers an optimized approach for the sensitive detection and quantification of low-target-abundance biological samples. DNA extraction will be planned on 1 mL of plasma, which will further increase the sensitivity of our technique initially based on only 200µL of DNA extracted plasma.

Keywords

Sequence: 80216350 Sequence: 80216351
Name HPV16 Name CtDNA
Downcase Name hpv16 Downcase Name ctdna

Design Outcomes

Sequence: 178345856 Sequence: 178345857 Sequence: 178345858 Sequence: 178345859 Sequence: 178345860 Sequence: 178345861 Sequence: 178345862 Sequence: 178345863 Sequence: 178345864
Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary
Measure Negative Predictive Value (NPV) of HPV16 ct-DNA Measure 5- year Negative Predictive Value Measure Positive Predictive Value (PPV) of HPV16 ct-DNA Measure Rate of relapses detected by HPV16 ct-DNA Measure Disease-free survival Measure Loco-Regional recurrence Measure Time of distant recurrence Measure Overall survival Measure Cost-effectiveness analysis of the proposed strategy
Time Frame 24 months Time Frame 48 and 60 months Time Frame 18, 24, 48, and 60 months Time Frame 5.5 years Time Frame 5.5 years Time Frame From randomization to disease recurrence, up to 5.5 years Time Frame From randomization to disease recurrence, up to 5.5 years Time Frame From randomization to death from any cause, up to 5.5 years Time Frame 5.5 years
Description The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results. Description The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results. Description The presence of HPV16 ct-DNA will be evaluated by ddPCR. PPV will be defined as 2 successive HPV16 ct-DNA positive results. Description The proportion of patients with relapse detected by HPV16 ct-DNA without any other symptoms. Description Disease-free survival (DFS) is defined as the delay between date of inclusion and tumor relapse (local, regional, or distant) or death from any cause, whichever occurs first. Description Evaluation of the stage of the first loco-regional event detected by medical imaging. The stage will be defined by the size of the tumor and the number of invaded lymph nodes. Description The length of time until manifestation of the first metastatic event detected by medical imaging. Description The overall survival is the length of time from randomization that patients enrolled in the study are still alive. Description To evaluate the economic cost of the lightened surveillance as compared to the standard treatment in terms of cost assessments and incremental cost-effectiveness ratio.

Browse Conditions

Sequence: 194464582 Sequence: 194464583 Sequence: 194464584 Sequence: 194464585 Sequence: 194464586 Sequence: 194464587 Sequence: 194464588 Sequence: 194464589 Sequence: 194464590 Sequence: 194464591 Sequence: 194464592 Sequence: 194464593
Mesh Term Oropharyngeal Neoplasms Mesh Term Recurrence Mesh Term Neoplasms Mesh Term Disease Attributes Mesh Term Pathologic Processes Mesh Term Pharyngeal Neoplasms Mesh Term Otorhinolaryngologic Neoplasms Mesh Term Head and Neck Neoplasms Mesh Term Neoplasms by Site Mesh Term Pharyngeal Diseases Mesh Term Stomatognathic Diseases Mesh Term Otorhinolaryngologic Diseases
Downcase Mesh Term oropharyngeal neoplasms Downcase Mesh Term recurrence Downcase Mesh Term neoplasms Downcase Mesh Term disease attributes Downcase Mesh Term pathologic processes Downcase Mesh Term pharyngeal neoplasms Downcase Mesh Term otorhinolaryngologic neoplasms Downcase Mesh Term head and neck neoplasms Downcase Mesh Term neoplasms by site Downcase Mesh Term pharyngeal diseases Downcase Mesh Term stomatognathic diseases Downcase Mesh Term otorhinolaryngologic diseases
Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48557379
Agency Class OTHER
Lead Or Collaborator lead
Name UNICANCER

Design Group Interventions

Sequence: 68500558
Design Group Id 55878592
Intervention Id 52737677

Eligibilities

Sequence: 30912842
Gender All
Minimum Age 18 Years
Maximum Age N/A
Healthy Volunteers No
Criteria Inclusion Criteria: Patient aged 18 years or over Patient with p16 positive Oropharyngeal squamous cell carcinoma (OPSCC) Clinical stage T1-4, N0-3, M0 (stages I-III) Any tobacco status Life expectancy greater than 36 months Positive HPV16 Ct-DNA measured before curative anticancer treatment Treated by any curative treatment Complete response at 3 months after end of treatment, which means: Undetectable HPV16 Ct-DNA and no residual disease on imaging (group A) or Undetectable HPV16 Ct-DNA and suspicious imaging but persistent disease excluded by either biopsy or repeated imaging (group B1) or Positive HPV16 Ct-DNA and no residual disease on imaging but negative HPV16 Ct-DNA on the subsequent assessment. This second test will be done 1-2 months after the first one (group C1). Patient must be affiliated to a Social Security System (or equivalent) Patients must have signed a written informed consent form prior to any trial specific procedures. If the patient is physically unable to give his/her written consent, a trusted person of his/her choice, note related to the investigator or the sponsor, can confirm in writing the patient's consent. Exclusion Criteria: Uncontrolled intercurrent illness that would limit compliance with study requirements. Active invasive malignancy within 3 years of inclusion except for non-invasive malignancies such as non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured. Any other HPV induced cancer within 5 years Any condition that may jeopardize the patient participation as well as non-contraception for male and female with child-bearing potential, pregnancy or breast-feeding Patient unwilling or unable to comply with the study protocol and follow-up schedule. Participation in another clinical trial with an investigational medical product during the last 30 days prior to the inclusion and during the present study (except if patient is included in the control arm, with placebo or with a product that have a marketed authorization, used as per the summary of product characteristics (SmPC) for the given indication). Patient deprived of liberty or placed under protective custody or guardianship.
Adult True
Child False
Older Adult True

Calculated Values

Sequence: 254175554
Registered In Calendar Year 2022
Were Results Reported False
Has Single Facility False
Minimum Age Num 18
Minimum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 8

Designs

Sequence: 30658539
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Diagnostic
Time Perspective
Masking None (Open Label)

Responsible Parties

Sequence: 29025210
Responsible Party Type Sponsor