HPV InfectionORGANOIDESNCT04278326
Primary Organoid Models and Combined Nucleic Acids Therapeutics for Anti-HPV Treatments
A study testing Vaginal Biopsy in people with HPV Infection and Vaginal Cancer, run by Centre Hospitalier Régional d'Orléans at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- HPV Infection, Vaginal Cancer, Cervical Dysplasia
- What is being tested?
- Vaginal Biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- 21 Dec 2021to 21 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- - 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- HPV Infection, Vaginal Cancer, Cervical Dysplasia, Cervical Cancer
- Being tested
- Vaginal Biopsy
- Keywords
- vaginal organoid, human papilloma virus, nucleic acids, cervical dysplasia, cervical cancer
- Medical subject headings
- Papillomavirus Infections, Vaginal Neoplasms, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal BiopsyProcedure or surgery
- Vaginal biopsies
- Additional cervical and vaginal biopsies
- Non invasive cervico-vaginal swab like a smear
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: Vaginal Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To develop a 3D vaginal organoid culture model.
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
Measured: 4 years
Secondary outcomes (1)
Inhibition of HPV molecular therapeutics using oligonucleotide, and siRNA (small interfering RNA)
To be able to use a vaginal cellular 3D model to develop an anti-HPV treatment
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2020
- Study start21 Dec 2021
- Primary completion21 Dec 2021
- Study completion21 Dec 2021
Why it stopped: the partner laboratory encountered various difficulties (COVID, relocation of the laboratory, personnel problems), which prevented the organoid model from being built
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HPV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Régional d'Orléans
- Sponsor type
- University, hospital or other
- Collaborators
- CNRS - Pr Chantal PICHON
- Responsible party
- Sponsor
- Investigators
- Souhail ALOUINI, M.D.,Ph.D., Principal investigator, CHR OrléansChantal PICHON, Ph.D., Study chair, Centre National de la Recherche Scientifique, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04278326
- Sponsor's protocol ID
- CHRO-2019-08
- Acronym
- ORGANOIDES
- Status last verified
- Apr 2025
- First submitted
- 18 Feb 2020
- Last updated
- 20 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ngamkham J, Boonmark K, Phansri T. Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women. Asian Pac J Cancer Prev. 2016;17(3):1129-34. doi: 10.7314/apjcp.2016.17.3.1129.
PubMed 27039737Duke P, Godwin M, Ratnam S, Dawson L, Fontaine D, Lear A, Traverso-Yepez M, Graham W, Ravalia M, Mugford G, Pike A, Fortier J, Peach M. Effect of vaginal self-sampling on cervical cancer screening rates: a community-based study in Newfoundland. BMC Womens Health. 2015 Jun 10;15:47. doi: 10.1186/s12905-015-0206-1.
PubMed 26060041Koo YJ, Min KJ, Hong JH, Lee JK. Efficacy of Poly-Gamma-Glutamic Acid in Women with High-Risk Human Papillomavirus-Positive Vaginal Intraepithelial Neoplasia: an Observational Pilot Study. J Microbiol Biotechnol. 2015 Jul;25(7):1163-9. doi: 10.4014/jmb.1503.03106.
PubMed 25907060Mollers M, King AJ, Knol MJ, Scherpenisse M, Meijer CJ, van der Klis FR, de Melker HE. Effectiveness of human papillomavirus vaccine against incident and persistent infections among young girls: Results from a longitudinal Dutch cohort study. Vaccine. 2015 May 28;33(23):2678-83. doi: 10.1016/j.vaccine.2015.04.016. Epub 2015 Apr 14.
PubMed 25887090Wang KD, Xu DJ, Wang BY, Yan DH, Lv Z, Su JR. Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells. Probiotics Antimicrob Proteins. 2018 Jun;10(2):236-242. doi: 10.1007/s12602-017-9339-x.
PubMed 29071554
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Primary Organoid Models and Combined Nucleic Acids Therapeutics for Innovative Anti-HPV Treatments in Cervico-vaginal Cancers and Precancerous Lesions
- ClinicalTrials.gov ID
- NCT04278326
- Acronym / sponsor ID
- ORGANOIDES / CHRO-2019-08
- Conditions
- HPV Infection, Vaginal Cancer, Cervical Dysplasia, Cervical Cancer
- Keywords
- vaginal organoid, human papilloma virus, nucleic acids, cervical dysplasia, cervical cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: the partner laboratory encountered various difficulties (COVID, relocation of the laboratory, personnel problems), which prevented the organoid model from being built
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Centre Hospitalier Régional d'OrléansUniversity, hospital or other
- Collaborators
- CNRS - Pr Chantal PICHON
- Study start
- 21 Dec 2021 (actual)
- Primary completion
- 21 Dec 2021 (actual)
- Study completion
- 21 Dec 2021 (actual)
- First posted
- 20 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Procedure: Vaginal Biopsy1. 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vaginal Biopsy1. Vaginal biopsies 2. Additional cervical and vaginal biopsies 3. Non invasive cervico-vaginal swab like a smear | Procedure or surgery | Experimental |
Primary outcome
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
1 secondary outcome
Inhibition of HPV molecular therapeutics using oligonucleotide, and siRNA (small interfering RNA)
Time frame: 4 years
Results and safety
The study was stopped early (reason given: the partner laboratory encountered various difficulties (COVID, relocation of the laboratory, personnel problems), which prevented the organoid model from being built). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2025.
- Background: PubMed 27039737Ngamkham J, Boonmark K, Phansri T. Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women. Asian Pac J Cancer Prev. 2016;17(3):1129-34. doi: 10.7314/apjcp.2016.17.3.1129.
- Background: PubMed 26060041Duke P, Godwin M, Ratnam S, Dawson L, Fontaine D, Lear A, Traverso-Yepez M, Graham W, Ravalia M, Mugford G, Pike A, Fortier J, Peach M. Effect of vaginal self-sampling on cervical cancer screening rates: a community-based study in Newfoundland. BMC Womens Health. 2015 Jun 10;15:47. doi: 10.1186/s12905-015-0206-1.
- Background: PubMed 25907060Koo YJ, Min KJ, Hong JH, Lee JK. Efficacy of Poly-Gamma-Glutamic Acid in Women with High-Risk Human Papillomavirus-Positive Vaginal Intraepithelial Neoplasia: an Observational Pilot Study. J Microbiol Biotechnol. 2015 Jul;25(7):1163-9. doi: 10.4014/jmb.1503.03106.
- Background: PubMed 25887090Mollers M, King AJ, Knol MJ, Scherpenisse M, Meijer CJ, van der Klis FR, de Melker HE. Effectiveness of human papillomavirus vaccine against incident and persistent infections among young girls: Results from a longitudinal Dutch cohort study. Vaccine. 2015 May 28;33(23):2678-83. doi: 10.1016/j.vaccine.2015.04.016. Epub 2015 Apr 14.
- Background: PubMed 29071554Wang KD, Xu DJ, Wang BY, Yan DH, Lv Z, Su JR. Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells. Probiotics Antimicrob Proteins. 2018 Jun;10(2):236-242. doi: 10.1007/s12602-017-9339-x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Souhail ALOUINI, M.D.,Ph.D. principal investigator
CHR Orléans
Chantal PICHON, Ph.D. study chair
Centre National de la Recherche Scientifique, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vaginal Biopsy in people with HPV Infection and Vaginal Cancer, run by Centre Hospitalier Régional d'Orléans at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: the partner laboratory encountered various difficulties (COVID, relocation of the laboratory, personnel problems), which prevented the organoid model from being built). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To develop a 3D vaginal organoid culture model. (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04278326, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2025.