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 (SURVEILLE-HPV)
SURVEILLE-HPV: National, Multicenter, Open-label, Randomized, Phase II Study Evaluating HPV16 Circulating DNA as Biomarker to Detect the Recurrence, in Order to Improve Post Therapeutic Surveillance of HPV16-driven Oropharyngeal Cancers
SURVEILLE-HPV - A new post therapeutic surveillance strategy for HPV-driven oropharyngeal cancer based on HPV Circulating DNA measures.
HPV-positive oropharyngeal cancer patients have a much better prognosis that their HPV-negative counterparts. Despite this, Post Treatment Surveillance (PTS) strategy does not take into account HPV status.
HPV Circulating DNA (HPV Ct DNA) has emerged as a promising tool to assess the risk of cancer recurrence following treatment. We assume that this biomarker could be helpful to guide PTS.
The number of systematic PTS visits could be significantly reduced in patients with undetectable HPV Ct DNA whereas a closer clinical and radiological follow up could be performed in case of detectable HPV Ct DNA.
If confirmed, this new strategy could have several benefits including:
- reduction of PTS visits for most HPV-positive patients which implies a potential cost decrease and
- Identification of relapse at early stages (before the occurrence of symptoms)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Avignon, France
- Recruiting
- ISC Avignon
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Contact:
- Benoit CALDERON
- Phone Number: 04 90 27 62 74
- Email: b.calderon@isc84.org
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Dijon, France
- Recruiting
- Georges-François Leclerc
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Contact:
- David THIBOUW
- Phone Number: 03 70 63 23 23
- Email: dthibouw@cgfl.fr
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Lille, France
- Not yet recruiting
- Oscar Lambret- Lille
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Contact:
- Samia BOUHIR
- Phone Number: 03 20 29 59 59
- Email: s.bouhir@o-lambret.fr
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Marseille, France
- Recruiting
- La Timone-AP-HM Marseille
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Contact:
- Sébastien SALAS
- Phone Number: 04 91 38 57 08
- Email: sebastien.salas@ap-hm.fr
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Nice, France
- Active, not recruiting
- Antoine Lacassagne - NICE
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Nîmes, France
- Active, not recruiting
- CHU De Nîmes ICG
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Paris, France
- Recruiting
- Hôpital Europeén Georges Pompidou
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Contact:
- Haïtham MIRGHANI
- Phone Number: 01 56 09 34 53
- Email: haitham.mirghani@aphp.fr
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Paris, France
- Not yet recruiting
- Institut Curie - Paris
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Contact:
- Joey MARTIN
- Phone Number: 06 89 65 30 29
- Email: joey.martin@curie.fr
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Paris, France
- Recruiting
- TENON - APHP Paris
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Contact:
- Bertrand BAUJAT
- Phone Number: 01 56 01 64 17
- Email: bertrand.baujat@aphp.fr
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Rennes, France
- Recruiting
- Eugène Marquis-Rennes
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Contact:
- Florian ESTRADE
- Phone Number: 02 99 25 31 82
- Email: f.estrade@rennes.unicancer.fr
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Saint-Herblain, France
- Not yet recruiting
- ICO - Site St Herblain
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Contact:
- Mélanie DORE
- Phone Number: 02 40 67 99 00
- Email: melanie.dore@ico.unicancer.fr
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Strasbourg, France
- Recruiting
- ICANS Strasbourg
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Contact:
- Mickaël BURGY
- Phone Number: 03 68 76 71 15
- Email: m.burgy@icans.eu
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Toulouse, France
- Recruiting
- IUCT Oncopole Toulouse
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Contact:
- Anouchka MODESTO
- Phone Number: 05 31 15 54 29
- Email: modesto.anouchka@iuct-oncopole.fr
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Vandœuvre-lès-Nancy, France
- Recruiting
- Institut de Cancérologie de Lorraine
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Contact:
- Romina MASTRONICOLA
- Phone Number: 03 83 59 83 04
- Email: r.mastronicola@nancy.unicancer.fr
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Villejuif, France
- Recruiting
- Gustave Roussy
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Contact:
- Pierre BLANCHARD
- Phone Number: 01 42 11 53 60
- Email: Pierre.BLANCHARD@gustaveroussy.fr
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La Réunion
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Saint-Denis, La Réunion, France
- Active, not recruiting
- Clinique St Vincent- Réunion
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
No Intervention: Standard follow-up monitoring (16 visits over 5 years)
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. |
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Experimental: Lightened follow-up visits frequency (9 visits over 5 years), with HPV16 Ct-DNA dosing
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:
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Negative Predictive Value (NPV) of HPV16 ct-DNA
Time Frame: 24 months
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The presence of HPV16 ct-DNA will be evaluated by ddPCR.
NPV will be defined as 2 successive HPV16 ct-DNA negative results.
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24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
5- year Negative Predictive Value
Time Frame: 48 and 60 months
|
The presence of HPV16 ct-DNA will be evaluated by ddPCR.
NPV will be defined as 2 successive HPV16 ct-DNA negative results.
|
48 and 60 months
|
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Positive Predictive Value (PPV) of HPV16 ct-DNA
Time Frame: 18, 24, 48, and 60 months
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The presence of HPV16 ct-DNA will be evaluated by ddPCR.
PPV will be defined as 2 successive HPV16 ct-DNA positive results.
|
18, 24, 48, and 60 months
|
|
Rate of relapses detected by HPV16 ct-DNA
Time Frame: 5.5 years
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The proportion of patients with relapse detected by HPV16 ct-DNA without any other symptoms.
|
5.5 years
|
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Disease-free survival
Time Frame: 5.5 years
|
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.
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5.5 years
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Loco-Regional recurrence
Time Frame: From randomization to disease recurrence, up to 5.5 years
|
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.
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From randomization to disease recurrence, up to 5.5 years
|
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Time of distant recurrence
Time Frame: From randomization to disease recurrence, up to 5.5 years
|
The length of time until manifestation of the first metastatic event detected by medical imaging.
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From randomization to disease recurrence, up to 5.5 years
|
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Overall survival
Time Frame: From randomization to death from any cause, up to 5.5 years
|
The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
|
From randomization to death from any cause, up to 5.5 years
|
|
Cost-effectiveness analysis of the proposed strategy
Time Frame: 5.5 years
|
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.
|
5.5 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UC-HNG-2209
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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