Oropharynx Squamous Cell Carcinoma
Conditions
Keywords
HPV16, CtDNA
Brief summary
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
BIOLOGICALHPV16 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 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.
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient aged 18 years or over 2. Patient with p16 positive Oropharyngeal squamous cell carcinoma (OPSCC) 3. Clinical stage T1-4, N0-3, M0 (stages I-III) 4. Any tobacco status 5. Life expectancy greater than 36 months 6. Positive HPV16 Ct-DNA measured before curative anticancer treatment 7. Treated by any curative treatment 8. 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). 9. Patient must be affiliated to a Social Security System (or equivalent) 10. 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
1. Uncontrolled intercurrent illness that would limit compliance with study requirements. 2. 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. 3. Any other HPV induced cancer within 5 years 4. 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 5. Patient unwilling or unable to comply with the study protocol and follow-up schedule. 6. 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). 7. Patient deprived of liberty or placed under protective custody or guardianship.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value (NPV) of HPV16 ct-DNA | 24 months | The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive Predictive Value (PPV) of HPV16 ct-DNA | 18, 24, 48, and 60 months | The presence of HPV16 ct-DNA will be evaluated by ddPCR. PPV will be defined as 2 successive HPV16 ct-DNA positive results. |
| Rate of relapses detected by HPV16 ct-DNA | 5.5 years | The proportion of patients with relapse detected by HPV16 ct-DNA without any other symptoms. |
| Disease-free survival | 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. |
| 5- year Negative Predictive Value | 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. |
| Time of distant recurrence | 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. |
| Overall survival | 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. |
| Cost-effectiveness analysis of the proposed strategy | 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. |
| Loco-Regional recurrence | 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. |
Countries
France
Outcome results
None listed