Primary Organoid Models and Combined Nucleic Acids Therapeutics for Anti-HPV Treatments (ORGANOIDES)

May 5, 2023 updated by: Centre Hospitalier Régional d'Orléans

Primary Organoid Models and Combined Nucleic Acids Therapeutics for Innovative Anti-HPV Treatments in Cervico-vaginal Cancers and Precancerous Lesions

Human papilloma virus (HPV) is responsible of the most common sexually transmitted infection. It can cause severe cancer lesions, of the cervix, vulva, vagina, penis and oropharynx. The International Agency for Cancer Research of World Health Organization (WHO) classified a dozen of HPV related high-risk cancer types, and recognized cervical cancer as the most common HPV-related disease. HPV 16 and 18 are responsible for 70% of cervical cancers.

Due to the few symptoms of cervical cancer, women are often diagnosed with advanced state. Current treatments imply cervical conisation or hysterectomy, with or without lymphadenectomy and or radiotherapy, or chemotherapy.

However, few pharmacological options are available against oncogenic papilloma viruses and thus against recurrences The aim of this project is to develop relevant organoids models from patient biopsies that will be used to identify biomarkers and evaluate in a closest preclinical setting novel nucleic acids based therapeutic strategy for HPV-cervical-vaginal dysplasia and cancers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this project, the investigators want to develop organotypic culture of primary-derived biopsies, and combine them with organ-on-a-chip technology, to better characterize the HPV infection and cancer progression, as well as to screen innovative treatments for cervical and vaginal cancers.

Our study will cover cervical dysplasia and cervical cancers HPV induced. The investigators will perform cervical and or vaginal biopsies from patients with oncogenic HPV lesions. A protocol validated to collect biopsies from precancerous cervico-vaginal lesions or cervical cancer patients in CHRO (Orleans, France). The biopsies will be performed during a consultation in the Hospital center of Orleans, or in the theatre room during a conisation or an hysterectomy. The PRIMMO platform is the research platform of Regional hospital center of Orleans (CHRO) dedicated to the promotion of translational research. It will be involved in the collection, analysis and biobank storage setup of the project. Fresh samples will be collected and bring directly to the lab for organoid cell culture development. Detection of HPV in each biopsy will be carried out by the PRIMMO platform.

The organoid development from patient biopsies will take place into the lab of the Biophysic Molecular center in Orleans.

The organoids will be selected according to three criteria: their ability to grow until a first passage, their doubling time and their ability to be frozen and resuscitated. Such organoids maintain pathogen-host interaction and better model physiopathology of vaginal cervical dysplasia CIN2-3 or cervical cancer and thus allow for the detection of biomarkers for pre-cancerous lesions. In addition, organoids reduce the use of animal models and can be used for drug screening, In a second step, the investigators propose to use mRNA to produce in situ the nanobodies targeting E6 and E7, to inhibit viral replication and tumor growth

Socio-epidemiological data will be collected for each patient, in the form of a table.

The study could be stopped in case of serious undesirable events. Safety evaluation As this is a category 2 study, no particular vigilance linked to the research protocol will be useful.

However, the monitoring and reporting of unexpected events resulting from participation in the study will be declared to the "materiovigilance site" of the CHR of Orleans Given the minimal risks associated with the study, an independent monitoring committee was not considered necessary.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients between 18 and 75 years old.
  • Patients presented with cervical or vaginal dysplasia or cancer induced by oncogenic HPV demonstrated by a PAP test and or HPV testing requiring a biopsy and histology in current care.

Patients with previous history of conisation or hysterectomy for lesions of the cervix or the vagina caused by oncogenic HPV.

To participate in the study, patients must sign an informed consent.

Exclusion Criteria:

  • - Pregnant women
  • Patients with coagulation disorders
  • Refusal of patients to participate in the trial Patients not affiliated to medical insurance
  • Person deprived of their liberty by judicial or administrative decision
  • Adults over 18 who are under legal protection measures or cannot give their consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
  1. Patients infected by oncogenic HPV and presented a high grade cervical dysplasia or a cervical cancer
  2. Patients with cervical or vaginal cancer
  3. All patients
Procedure: Vaginal Biopsy
  1. Vaginal biopsies
  2. Additional cervical and vaginal biopsies
  3. Non invasive cervico-vaginal swab like a smear

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To develop a 3D vaginal organoid culture model.
Time Frame: 4 years
The main objective is to develop a 3D cell culture model of organoid type from vaginal and cervical biopsies of patients infected with an oncogenic papilloma virus
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inhibition of HPV molecular therapeutics using oligonucleotide, and siRNA (small interfering RNA)
Time Frame: 4 years
To be able to use a vaginal cellular 3D model to develop an anti-HPV treatment
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Régional d'Orléans

Collaborators

CNRS - Pr Chantal PICHON

Investigators

  • Principal Investigator: Souhail ALOUINI, M.D.,Ph.D., CHR Orléans
  • Study Chair: Chantal PICHON, Ph.D., Centre National de la Recherche Scientifique, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2020

Primary Completion (Anticipated)

April 1, 2024

Study Completion (Anticipated)

April 1, 2024

Study Registration Dates

First Submitted

February 18, 2020

First Submitted That Met QC Criteria

February 18, 2020

First Posted (Actual)

February 20, 2020

Study Record Updates

Last Update Posted (Estimate)

May 8, 2023

Last Update Submitted That Met QC Criteria

May 5, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHRO-2019-08

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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