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

Official title

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

Overview

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)

Interventions

• Biological HPV16 Ct-DNA dosing
  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 compa

Primary outcome measures

• Negative Predictive Value (NPV) of HPV16 ct-DNA [Time frame: 24 months]

Secondary outcome measures (8)

• 5- year Negative Predictive Value [Time frame: 48 and 60 months]
• Positive Predictive Value (PPV) of HPV16 ct-DNA [Time frame: 18, 24, 48, and 60 months]
• Rate of relapses detected by HPV16 ct-DNA [Time frame: 5.5 years]
• Disease-free survival [Time frame: 5.5 years]
• Loco-Regional recurrence [Time frame: From randomization to disease recurrence, up to 5.5 years]
• Time of distant recurrence [Time frame: From randomization to disease recurrence, up to 5.5 years]
• Overall survival [Time frame: From randomization to death from any cause, up to 5.5 years]
• Cost-effectiveness analysis of the proposed strategy [Time frame: 5.5 years]

Eligibility 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 16 centers

• Clinique St Vincent- Réunion — Saint-Denis
• ISC Avignon — Avignon
• Georges-François Leclerc — Dijon
• Oscar Lambret- Lille — Lille
• La Timone-AP-HM Marseille — Marseille
• Antoine Lacassagne - NICE — Nice
• CHU De Nîmes ICG — Nîmes
• Hôpital Européen Georges Pompidou — Paris
• … and 8 more centers

Identifiers

NCT: NCT05582122 · UC-HNG-2209

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗