CIN2NCT04687267
Conservative Management of CIN2 Lesions and Biomarkers Evaluation
An observational study of CIN2, run by Istituto Oncologico Veneto IRCCS at 4 sites in Italy.
Trial summary
Prospective study including women aged 25-45 years, adherent to the cervical screening program of four different centers of the Veneto region, with a diagnosis of CIN2 lesion. After enrollment according to predefined criteria, and informed consent to participate, the CIN2 lesions are managed by follow-up; cases with… Read more about this study
- Who is it for?
- Ages 25 to 45 years, women only
- Conditions the study is for
- CIN2
- How many people
- 319 participants
- Where
- 4 sitesItaly
- Study dates
- 15 Apr 2019to 31 Dec 2022
- Phase
- Observational
- 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 25 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Women attending organized population-based cervical cancer screening with a histological CIN2 lesion, meeting the selection criteria and consenting to participate.
Who may be able to join
- age range 25-45 years,
- CIN2 lesions located in the exocervix and completely visible at colposcopy.
Who cannot join
- age >45 years;
- history of previous high-grade lesions;
- squamo-columnar junction not completely visible (type 3);
- cytology with suspect or indicative for invasive lesion;
- lesions exclusively located in the endocervix;
- lesions located in the exocervix but not completely visible;
- pregnancy
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Azienda ULSS 3 Serenissima
Mestre, VE
Azienda ULSS 6 Euganea
Padova, PD
Azienda ULSS 2 Marca Trevigiana
Treviso, TV
Azienda ULSS 9 Scaligera
Verona, VR
About this study
Official title: Gestione Conservativa di Lesioni CIN2 e Valutazione di Biomarcatori Indicativi di Regressione
Prospective study including women aged 25-45 years, adherent to the cervical screening program of four different centers of the Veneto region, with a diagnosis of CIN2 lesion. After enrollment according to predefined criteria, and informed consent to participate, the CIN2 lesions are managed by follow-up; cases with progressive lesions will be treated immediately, cases with CIN2 persistence for more than 12 months will be treated as well. Viral, molecular and immunocytochemical biomarkers will be studied, and evaluated in relation to the clinical outcome.
Read the detailed description
Women aged 25-45 years, adherent to the organized population-based cervical screening program, with a histological diagnosis of CIN2 and fulfilling the inclusion criteria will be invited to participate to the study, previously providing specific information; in case of acceptance, informed consent is signed.
STUDY PROTOCOL:
The adherent women will attend periodical control visits:
- every 6 months up to 24 months, with performance of: pap test (PT) and colposcopy (with biopsy in case of visible alterations);
- at 6 and 12 months control visit: a liquid-based sample of cervical cells will be collected for the biomarkers' analyses.
BIOMARKERS:
- - HPV search and partial HPV16/18 genotyping, by cobas 4800 high-risk HPV assay (Roche); PCR with MY09/MY11 consensus primers and full genotyping by restriction fragment length analysis, plus PCR with beta-globin primers (in-house);
- - methylation analysis of the cellular genes FAM194A and hsa-mir124-2, by methylation-specific quantitative PCR test (qMSP - QIAsure methylation test, Qiagen);
- - methylation analysis of the L1 and L2 viral genes of HPV types 16 and 18, by pyrosequencing;
- - immunocytochemical analysis for p16INK4A/Ki67 proteins (dual stain), by p16INK4A/Ki67 immunocytochemical analysis by CINtec Plus kit (Roche).
- Conditions
- CIN2
- Keywords
- biomarkers, HPV, methylation, clinical outcome
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of spontaneous regression of CIN2 lesions
Eligible women will not be treated at diagnosis, but periodically followed-up. Treatment will be provided for progressive lesions and lesions persisting more than 12 months. The rates of lesion regression will be calculated: number of lesions regressed to CIN1 or normal / total number of cases.
Measured: Through study completion, an average of 2 years.
CIN2 clinical outcome by HPV genotype
Rate of CIN2 regression will be calculated in relation to positivity for HPV16 vs positivity for other high-risk types (number of regressed HPV16-related CIN2 lesions / total number of HPV16-related CIN2 vs number of regressed non-HPV16-related CIN2 lesions / total number of non-HPV16-related CIN2 lesions).
Measured: Through study completion, an average of 2 years.
CIN2 clinical outcome by DNA methylation
Rate of CIN2 regression will be calculated in relation to DNA methylation of cellular and viral genes (number of regressed hypermethylated CIN2 lesions / total number of CIN2 lesions with valid result for each gene analyzed).
Measured: Through study completion, an average of 2 years.
CIN2 clinical outcome by p16/ki67 protein expression
Rate of CIN2 regression will be calculated in relation to positivity for p16/ki67 expression (number of regressed p16/ki67-positive CIN2 lesions / total number of CIN2 lesions with valid result for p16/ki67 expression).
Measured: Through study completion, an average of 2 years.
Secondary outcomes (1)
Adhesion to CIN2 conservative management.
The rate of eligible women consenting to participate to the study will be calculated (enrolled women / eligible women)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2020
- Study start15 Apr 2019
- Primary completion31 Oct 2021
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CIN2Studies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 319 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Oncologico Veneto IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda ULSS 3 Serenissima, Azienda Ulss 6 Euganea, Azienda Ulss 2 Marca Trevigiana, Azienda Ulss 9 Scaligera, Regione Veneto
- Responsible party
- Principal investigator, Annarosa Del Mistro, Istituto Oncologico Veneto IRCCS
- Investigators
- Tiziano Maggino, MD, Principal investigator, Azienda ULSS 3 Serenissima
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04687267
- Sponsor's protocol ID
- CIN2-RSFR
- Status last verified
- Sep 2023
- First submitted
- 10 Dec 2020
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Del Mistro A, Matteucci M, Insacco EA, Onnis G, Da Re F, Baboci L, Zorzi M, Minucci D. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study. Biomed Res Int. 2015;2015:984528. doi: 10.1155/2015/984528. Epub 2015 Jun 9.
PubMed 26180819Del Mistro A, Frayle H, Rizzi M, Fantin G, Ferro A, Angeletti PM, Giorgi Rossi P, Altobelli E. Methylation analysis and HPV genotyping of self-collected cervical samples from women not responding to screening invitation and review of the literature. PLoS One. 2017 Mar 6;12(3):e0172226. doi: 10.1371/journal.pone.0172226. eCollection 2017.
PubMed 28263992Ordi J, Sagasta A, Munmany M, Rodriguez-Carunchio L, Torne A, del Pino M. Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathol. 2014 Mar;122(3):227-35. doi: 10.1002/cncy.21366.
PubMed 24757722Gillio-Tos A, Fiano V, Grasso C, Trevisan M, Gori S, Mongia A, De Marco L, Ronco G; New Technologies for Cervical Cancer Screening (NTCC) Working Group. Assessment of viral methylation levels for high risk HPV types by newly designed consensus primers PCR and pyrosequencing. PLoS One. 2018 Mar 26;13(3):e0194619. doi: 10.1371/journal.pone.0194619. eCollection 2018.
PubMed 29579066
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gestione Conservativa di Lesioni CIN2 e Valutazione di Biomarcatori Indicativi di Regressione
- ClinicalTrials.gov ID
- NCT04687267
- Acronym / sponsor ID
- CIN2-RSFR
- Conditions
- CIN2
- Keywords
- biomarkers, HPV, methylation, clinical outcome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- Istituto Oncologico Veneto IRCCSUniversity, hospital or other
- Collaborators
- Azienda ULSS 3 Serenissima, Azienda Ulss 6 Euganea, Azienda Ulss 2 Marca Trevigiana, Azienda Ulss 9 Scaligera, Regione Veneto
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 29 Dec 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.
Prospective study including women aged 25-45 years, adherent to the cervical screening program of four different centers of the Veneto region, with a diagnosis of CIN2 lesion. After enrollment according to predefined criteria, and informed consent to participate, the CIN2 lesions are managed by follow-up; cases with progressive lesions will be treated immediately, cases with CIN2 persistence for more than 12 months will be treated as well. Viral, molecular and immunocytochemical biomarkers will be studied, and evaluated in relation to the clinical outcome.
Detailed description
Women aged 25-45 years, adherent to the organized population-based cervical screening program, with a histological diagnosis of CIN2 and fulfilling the inclusion criteria will be invited to participate to the study, previously providing specific information; in case of acceptance, informed consent is signed.
STUDY PROTOCOL:
The adherent women will attend periodical control visits:
- every 6 months up to 24 months, with performance of: pap test (PT) and colposcopy (with biopsy in case of visible alterations);
- at 6 and 12 months control visit: a liquid-based sample of cervical cells will be collected for the biomarkers' analyses.
BIOMARKERS:
- - HPV search and partial HPV16/18 genotyping, by cobas 4800 high-risk HPV assay (Roche); PCR with MY09/MY11 consensus primers and full genotyping by restriction fragment length analysis, plus PCR with beta-globin primers (in-house);
- - methylation analysis of the cellular genes FAM194A and hsa-mir124-2, by methylation-specific quantitative PCR test (qMSP - QIAsure methylation test, Qiagen);
- - methylation analysis of the L1 and L2 viral genes of HPV types 16 and 18, by pyrosequencing;
- - immunocytochemical analysis for p16INK4A/Ki67 proteins (dual stain), by p16INK4A/Ki67 immunocytochemical analysis by CINtec Plus kit (Roche).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Women attending organized population-based cervical cancer screening with a histological CIN2 lesion, meeting the selection criteria and consenting to participate.
Key inclusion criteria (2 listed)
- age range 25-45 years,
- CIN2 lesions located in the exocervix and completely visible at colposcopy.
Key exclusion criteria (7 listed)
- age >45 years;
- history of previous high-grade lesions;
- squamo-columnar junction not completely visible (type 3);
- cytology with suspect or indicative for invasive lesion;
- lesions exclusively located in the endocervix;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rate of spontaneous regression of CIN2 lesions
Time frame: Through study completion, an average of 2 years.
Eligible women will not be treated at diagnosis, but periodically followed-up. Treatment will be provided for progressive lesions and lesions persisting more than 12 months. The rates of lesion regression will be calculated: number of lesions regressed to CIN1 or normal / total number of cases.
CIN2 clinical outcome by HPV genotype
Time frame: Through study completion, an average of 2 years.
Rate of CIN2 regression will be calculated in relation to positivity for HPV16 vs positivity for other high-risk types (number of regressed HPV16-related CIN2 lesions / total number of HPV16-related CIN2 vs number of regressed non-HPV16-related CIN2 lesions / total number of non-HPV16-related CIN2 lesions).
CIN2 clinical outcome by DNA methylation
Time frame: Through study completion, an average of 2 years.
Rate of CIN2 regression will be calculated in relation to DNA methylation of cellular and viral genes (number of regressed hypermethylated CIN2 lesions / total number of CIN2 lesions with valid result for each gene analyzed).
CIN2 clinical outcome by p16/ki67 protein expression
Time frame: Through study completion, an average of 2 years.
Rate of CIN2 regression will be calculated in relation to positivity for p16/ki67 expression (number of regressed p16/ki67-positive CIN2 lesions / total number of CIN2 lesions with valid result for p16/ki67 expression).
1 secondary outcome
Adhesion to CIN2 conservative management.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Background: PubMed 26180819Del Mistro A, Matteucci M, Insacco EA, Onnis G, Da Re F, Baboci L, Zorzi M, Minucci D. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study. Biomed Res Int. 2015;2015:984528. doi: 10.1155/2015/984528. Epub 2015 Jun 9.
- Background: PubMed 28263992Del Mistro A, Frayle H, Rizzi M, Fantin G, Ferro A, Angeletti PM, Giorgi Rossi P, Altobelli E. Methylation analysis and HPV genotyping of self-collected cervical samples from women not responding to screening invitation and review of the literature. PLoS One. 2017 Mar 6;12(3):e0172226. doi: 10.1371/journal.pone.0172226. eCollection 2017.
- Background: PubMed 24757722Ordi J, Sagasta A, Munmany M, Rodriguez-Carunchio L, Torne A, del Pino M. Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathol. 2014 Mar;122(3):227-35. doi: 10.1002/cncy.21366.
- Background: PubMed 29579066Gillio-Tos A, Fiano V, Grasso C, Trevisan M, Gori S, Mongia A, De Marco L, Ronco G; New Technologies for Cervical Cancer Screening (NTCC) Working Group. Assessment of viral methylation levels for high risk HPV types by newly designed consensus primers PCR and pyrosequencing. PLoS One. 2018 Mar 26;13(3):e0194619. doi: 10.1371/journal.pone.0194619. eCollection 2018.
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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.
Tiziano Maggino, MD principal investigator
Azienda ULSS 3 Serenissima
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CIN2, run by Istituto Oncologico Veneto IRCCS at 4 sites in Italy.
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 2 inclusion and 7 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: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of spontaneous regression of CIN2 lesions (time frame: Through study completion, an average of 2 years.). The study lists 4 primary outcomes in all. 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 NCT04687267, which also lists 4 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 28 Sep 2023.