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

Oropharynx Squamous Cell Carcinoma Clinical Trial

— SURVEILLE-HPV  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05582122
• Other study ID #: UC-HNG-2209
• Status: Recruiting
• Phase: Phase 2
• Start date: April 3, 2024
• Est. completion date: April 1, 2031

Study information

• Verified date: April 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: April 1, 2031
• Est. primary completion date: April 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Oropharyngeal Neoplasms
• Oropharynx Squamous Cell Carcinoma
• Recurrence

Intervention

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 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.

Locations

Country	Name	City	State
France	ISC Avignon	Avignon
France	Georges-François Leclerc	Dijon
France	Oscar Lambret- Lille	Lille
France	La Timone-AP-HM Marseille	Marseille
France	Antoine Lacassagne - NICE	Nice
France	CHU De Nîmes ICG	Nîmes
France	Hôpital Européen Georges Pompidou	Paris
France	Institut Curie - Paris	Paris
France	TENON - APHP Paris	Paris
France	Eugène Marquis-Rennes	Rennes
France	Clinique St Vincent- Réunion	Saint-Denis	La Réunion
France	ICO - Site St Herblain	Saint-Herblain
France	ICANS Strasbourg	Strasbourg
France	IUCT Oncopole Toulouse	Toulouse
France	Institut de cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Negative Predictive Value (NPV) of HPV16 ct-DNA	The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results.	24 months
Secondary	5- year Negative Predictive Value	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
Secondary	Positive Predictive Value (PPV) of HPV16 ct-DNA	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
Secondary	Rate of relapses detected by HPV16 ct-DNA	The proportion of patients with relapse detected by HPV16 ct-DNA without any other symptoms.	5.5 years
Secondary	Disease-free survival	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.	5.5 years
Secondary	Loco-Regional recurrence	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.	From randomization to disease recurrence, up to 5.5 years
Secondary	Time of distant recurrence	The length of time until manifestation of the first metastatic event detected by medical imaging.	From randomization to disease recurrence, up to 5.5 years
Secondary	Overall survival	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
Secondary	Cost-effectiveness analysis of the proposed strategy	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