Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT01837693
Other study ID # cervicalscreening_mRNA_p16
Secondary ID
Status Not yet recruiting
Phase N/A
First received April 18, 2013
Last updated April 18, 2013
Start date June 2013
Est. completion date December 2019

Study information

Verified date May 2012
Source Azienda Unità Sanitaria Locale Reggio Emilia
Contact Enza Di Felice
Email difelicee@ausl.re.it
Is FDA regulated No
Health authority Italy: Ministry of Health
Study type Interventional

Clinical Trial Summary

In industrialized countries, cervical cancer is a well controlled disease thanks to the diffusion of Pap test and, in particular, to organized screening programs, which are able to detect and treat pre-invasive lesions (cervical intraepithelial neoplasia, CIN). The human papilloma virus (HPV) has been recognised as the necessary, but not sufficient, cause of cervical cancer, so a new screening test based on the identification of high risk (HR) HPV types has been developed(HPV DNA test). This test has demonstrated to be more effective than cytology in reducing the incidence and the mortality of cervical cancer, but it is less specific, so the use of a test triage is necessary to reduce the number of colposcopies and the risk of over-diagnosis (due to the potential regressivity of pre-invasive lesions). Until now, the triage test used is the cytology (Pap test).

Recently specific biomarkers (mRNA and p16 tests) have been introduced for high grade CIN, targeting the molecular alterations strictly associated to transformation rather than simply detecting HR-HPV infections. These tests are more specific than HPV DNA test with a modest reduction of sensitivity for high-grade lesions.

This is a multicenter randomised trial nested into some Italian screening programs based on the use of HPV DNA test as primary test.

All women with positive HPV DNA test will be tested for cytology and also for mRNA and p16. Women with positive cytology will be referred to colposcopy, while women with negative cytology will be randomized into two arms.

This study aims to evaluate if mRNA and p16 could be used as test of triage of HPV DNA or as a primary screening test with direct sending in colposcopy.

In particular the main objectives are:

- Measuring the cumulative detection rate of CIN2+ in the five years following a HPV DNA positive test and mRNA or p16 negative.

- Measuring the potential reduction of overdiagnosis of using mRNA or p16 test instead of DNA, with direct sending in colposcopy

- Measuring the reduction of overdiagnosis of cytological triage or triage with mRNA or p16 compared to the direct sending in colposcopy in women with HPV DNA test positive.

Secondary objectives are:

- to assess the feasibility of mRNA testing in primary screening

- to validate the sample techniques for the new tests

- to standardize quality controls for the the new tests


Description:

Individual data about the following study steps are collected according a fixed format:

1. recruited women

2. HPV DNA result

3. cytology and randomization results

4. p16 result

5. mRNA result

6. colposcopies (with relative cytology and histologies) results

7. Women excluded after informed consent

8. Interventions During the first year of recruitment, there will be two semi-annual sending of data, then each year.

To analyze the study progress in each center, summary tables will periodically send to the PI.

All CIN lesions and cancers found in the study will be be blindly reviewed. A set of quality assurance procedures will be implemented for both the molecular tests, including the use of controls provided by the manufacturers with known HPV DNA or mRNA content and the circulation of clinical samples prepared by the laboratories participating in the study.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 60000
Est. completion date December 2019
Est. primary completion date June 2015
Accepts healthy volunteers No
Gender Female
Age group 25 Years to 59 Years
Eligibility Inclusion Criteria:

- women invited for a new screening round based on HPV DNA test

Exclusion Criteria:

- women not resident in the screening area, or pregnant, or with treated CIN in the 5 previous years, or in post-colposcopy follow up, or in repetition for unsatisfactory cytology.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Screening


Intervention

Procedure:
Experimental: immediate colposcopy
A immediate colposcopy in this arm may detect potentially spontaneous regressive cervical lesions, so may determine an over diagnosis and over treatment, which the study want to estimate

Locations

Country Name City State
Italy Unità Locale Socio-Sanitaria 17 Este Monselice Este
Italy Istituto per lo Studio e la Prevenzione Oncologica Florence
Italy Azienda Sanitaria Locale 1-L'Aquila L'Aquila
Italy Istituto Oncologico Veneto Padua
Italy Azienda Sanitaria Locale 2- Regione Umbria Perugia
Italy Azienda Sanitaria Locale Reggio Emilia Reggio Emilia
Italy Laziosanità - Agenzia di Sanità Pubblica della Regione Lazio Rome
Italy Regina Elena Cancer Institute Rome
Italy Azienda Sanitaria Locale Roma G Tivoli
Italy Azienda Sanitaria della Provincia Autonoma di Trento Trento
Italy Centro per la Prevenzione Oncologica del Piemonte Turin

Sponsors (1)

Lead Sponsor Collaborator
Azienda Unità Sanitaria Locale Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary cumulative incidence of CIN2+ in women with positive DNA and negative mRNA or p16 Sum of CIN2+ detected in women with positive DNA and negative mRNA or p16 tests during the entire period (5 years) divided by the total number of CIN2+ found in the study. The HPV DNA test will be the final follow-up test, since it is the most sensitive test among the candidates for screening, so it is the one that allows to estimate more accurately the prevalence of lesions. 5 years No
Secondary comparison between CIN2+ detection rates in the two arms in women with p16 or mRNA negative proportion of CIN2+, HPV DNA positive and p16 or mRNA negative, which regress in a year 1 year Yes
Secondary comparison between CIN2+ detection rates in the two arms in women with negative cytology measure of how much the cytological triage can reduce overdiagnosis compared to HPV DNA with direct sending to colposcopy 1 year Yes
Secondary comparison between CIN2+ detection rate in the two arms in women with p16 or mRNA positive direct comparison of the effectiveness between a screening based on the HPV mRNA or p16 test followed by cytological triage and a screening with direct sending to colposcopy 1 year Yes
See also
  Status Clinical Trial Phase
Completed NCT03826043 - THrombo-Embolic Event in Onco-hematology N/A
Terminated NCT03166631 - A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread Phase 1
Completed NCT01938846 - BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors Phase 1
Recruiting NCT06058312 - Individual Food Preferences for the Mediterranean Diet in Cancer Patients N/A
Completed NCT03308942 - Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants Phase 2
Recruiting NCT06018311 - Exercising Together for Hispanic Prostate Cancer Survivor-Caregiver Dyads N/A
Withdrawn NCT05431439 - Omics of Cancer: OncoGenomics
Completed NCT01343043 - A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma Phase 1
Completed NCT01938638 - Open Label Phase I Dose Escalation Study With BAY1143572 in Patients With Advanced Cancer Phase 1
Recruiting NCT05514444 - Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001) Phase 1
Recruiting NCT02292641 - Beyond TME Origins N/A
Terminated NCT00954512 - Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004) Phase 1/Phase 2
Recruiting NCT04958239 - A Study to Test Different Doses of BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors) Phase 1
Recruiting NCT04627376 - Multimodal Program for Cancer Related Cachexia Prevention N/A
Completed NCT01222728 - Using Positron Emission Tomography to Predict Intracranial Tumor Growth in Neurofibromatosis Type II Patients
Recruiting NCT06004440 - Real World Registry for Use of the Ion Endoluminal System
Active, not recruiting NCT05636696 - COMPANION: A Couple Intervention Targeting Cancer-related Fatigue N/A
Not yet recruiting NCT06035549 - Resilience in East Asian Immigrants for Advance Care Planning Discussions N/A
Recruiting NCT06004466 - Noninvasive Internal Jugular Venous Oximetry
Not yet recruiting NCT02806557 - Profiling Neutrophil Counts in Patients on Chemotherapy N/A