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High Grade Intraepithelial NeoplasiaPhase 2NCT03233412

Randomized Clinical Trial Evaluating the Efficacy of Topical Imiquimod in High Grade Cervical Intraepithelial Lesions

A Phase 2 study testing Imiquimod in people with High Grade Intraepithelial Neoplasia and Cervix Cancer, run by Barretos Cancer Hospital at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Cervical cancer is one of the leading malignancies affecting women, with 311,000 deaths in 2018, most of them seen in underdeveloped countries. This neoplasm has a pre-invasive state, such as cervical intraepithelial neoplasia (CIN), which is caused by HPV (Human Papillomavirus) infection. Read more about this study

Who is it for?
Ages 25 to 50 years, women only
What is being tested?
Imiquimod
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteBrazil
Study dates
1 Jan 2018to 14 Jan 2020
Phase
Phase 2
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 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Women between the ages of 25 and 50 with histological diagnosis of CIN 2/3;
  • Living 300 km or less from the city of Barretos-São Paulo / Brazil.

Who cannot join

  • Suspected adenocarcinoma (in situ or invasive) or invading squamous cell carcinoma by colposcopy and/or citology;
  • Being pregnant or breastfeeding;
  • Women with some immunodeficiency or transplanted;
  • Previous treatment history for CIN 2/3.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Barretos Cancer Hospital

    Barretos

Other trials in Brazil

About this study

Official title: Ensaio clínico Randomizado Avaliando a eficácia do Tratamento tópico Com Imiquimode em lesões Intraepiteliais Cervicais de Alto Grau

Cervical cancer is one of the leading malignancies affecting women, with 311,000 deaths in 2018, most of them seen in underdeveloped countries. This neoplasm has a pre-invasive state, such as cervical intraepithelial neoplasia (CIN), which is caused by HPV (Human Papillomavirus) infection. The female organism most often is able to eliminate the virus, especially in young patients. However, when the infection becomes persistent, especially for subtypes 16 and 18, the risk of CIN developing an increased. Cytological screening programs can efficiently and wirelessly do this. As high-grade intraepithelial lesions (CIN 2/3) are as demonstrated by worse regression rate, only 13.3% at one year, and higher risk for progression to invasive cancer. As CIN 2/3 need treatment, and as more therapies as they are excisional, which theoretically are better, however, they may compromise the reproductive future of women who are unthreatened, increasing the risk of preterm labor, premature rupture of amniotic membranes, low weight Birth and perinatal mortality. This relationship aroused interest in seeking alternative therapies. Decrease antiviral activity directed against HPV, associated with a higher rate of elimination of the infection. Immediate, an agent that stimulates like dendritic cells to producer cytokines and activates epithelial T cells. Imiquimode, when used in vulvar neoplasias, has been shown to be effective, presenting satisfactory results without treatment of CIN 2/3 of the uterine cervix, requiring a better scientific compilation. Based on these data, this study aims to evaluate the efficacy of topical immunomodulatory treatment for high-grade cervical intraepithelial lesions.

Being tested
Control, Imiquimod
Keywords
high grade cervical intraepithelial neoplasia, Immunomodulatory treatment
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ControlProcedure or surgery

    Also called loop electrosurgical excision procedure, Conization of the cervix

    Exertion of the cervix transformation zone

  • ImiquimodDrug

    Also called Imiquimod 5% cream, Ixium 5%

    Application by the doctor of immunomodulatory cream on the uterine cervix 1 time per week for 12 weeks

Study groups in NCT03233412
Study groupRoleWhat they receive
ControlOtherWill be offered the standard treatment, which is the conization of the uterine cervix with loop electrosurgical excision procedure (LEEP).
Receives: Procedure: Control
ImiquimodExperimentalWill receive topical uterine cervix (Imiquimod) treatment for a period of 12 weeks with weekly applications (1x / week). 30-60 days afterwards they will be submitted to standard treatment with conization of the uterine cervix with loop electrosurgical excision procedure (LEEP).
Receives: Procedure: Control; Drug: Imiquimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of immunomodulatory treatment with Imiquimod in high grade intraepithelial lesions of the cervix compared to standard electrosurgical excision procedure (LEEP) treatment.

    We will evaluate the efficacy of the Imiquimod treatment applied by the physician after histological examination of the uterine cervix obtained by electrosurgical excision procedure (LEEP) and compare the rate of relapse / reoperation with the control patient only submitted to the standard treatment with LEEP

    Measured: 30 months

Secondary outcomes (6)

  1. Local and systemic adverse events

    To assess the local and systemic adverse effects of topical immunomodulatory treatment through anamnesis and physical examination.

    Measured: 30 months

  2. Compare CIN 2 and CIN 3 for the difference in response to immunomodulatory treatment

    It will be evaluated separately from the results of the treatment response with Imiquimod in CIN 2 and CIN 3 lesions.

    Measured: 30 months

  3. Definition of the difference in cost from actual standard treatment compared to Imiquimod

    The value in Brazilian reais of treatment with Imiquimod will be defined as compared to the amount spent for the standard treatment with LEEP

    Measured: 30 months

  4. Evaluation of recurrence of high grade cervical squamous intraepithelial lesion after 2 years of treatment.

    To evaluate the recurrence after 2 years of the end of the immunomodulatory topical treatment.

    Measured: 24 months

  5. Evaluation of reoperation rate after immunomodulatory treatment associated with standard treatment with LEEP compared to LEEP alone.

    Evaluation of reoperation rate in post-treatment follow-up.

    Measured: 24 months

  6. Clearance HPV

    To evaluate the persistence or not of the HPV virus and which specific type to relate to the efficacy of the immunomodulatory treatment.

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2017
  2. Study start1 Jan 2018
  3. Primary completion14 Jan 2020
  4. Study completion14 Jan 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients between 25 and 50 years old with histological diagnosis of high-grade intraepithelial lesion, obtained through satisfactory colposcopy and without previous treatment, who will be selected in the preventive clinic of the Hospital de Cancer de Barretos-SP (HCB ). Eligible patients will be identified at the return visit, when they will come to the hospital to check the result of the examination. In this study the patients will be randomized into two groups: Group 1: Control, where standard treatment will be offered, which is the conization of the uterine cervix with loop electrosurgical excision procedure(LEEP); Group 2: experimental group, which will receive topical treatment in the uterine cervix with immunomodulator (Imiquimod), for a period of 12 weeks, with weekly applications (1x / week). 30 to 60 days after immunomodulatory treatment the patient will be submitted to standard treatment with cervical conization with LEEP.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03233412
Sponsor's protocol ID
BarretosCH-20171
Status last verified
Apr 2019
First submitted
6 Jul 2017
Last updated
17 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • American College of Obstetricians and Gynecologists. Practice Bulletin No. 140: management of abnormal cervical cancer screening test results and cervical cancer precursors. Obstet Gynecol. 2013 Dec;122(6):1338-67. doi: 10.1097/01.AOG.0000438960.31355.9e. No abstract available.

    PubMed 24264713

  • Martin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO, Keep SL. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD001318. doi: 10.1002/14651858.CD001318.pub2.

    PubMed 20556751

  • Lin CT, Qiu JT, Wang CJ, Chang SD, Tang YH, Wu PJ, Jung SM, Huang CC, Chou HH, Jao MS, Lai CH. Topical imiquimod treatment for human papillomavirus infection in patients with and without cervical/vaginal intraepithelial neoplasia. Taiwan J Obstet Gynecol. 2012 Dec;51(4):533-8. doi: 10.1016/j.tjog.2012.09.006.

    PubMed 23276555

  • Pachman DR, Barton DL, Clayton AC, McGovern RM, Jefferies JA, Novotny PJ, Sloan JA, Loprinzi CL, Gostout BS. Randomized clinical trial of imiquimod: an adjunct to treating cervical dysplasia. Am J Obstet Gynecol. 2012 Jan;206(1):42.e1-7. doi: 10.1016/j.ajog.2011.06.105. Epub 2011 Jul 13.

    PubMed 21907959

  • McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008 May;9(5):425-34. doi: 10.1016/S1470-2045(08)70103-7. Epub 2008 Apr 11.

    PubMed 18407790

  • Arbyn M, Kyrgiou M, Simoens C, Raifu AO, Koliopoulos G, Martin-Hirsch P, Prendiville W, Paraskevaidis E. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008 Sep 18;337:a1284. doi: 10.1136/bmj.a1284.

    PubMed 18801868

  • Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006 Feb 11;367(9509):489-98. doi: 10.1016/S0140-6736(06)68181-6.

    PubMed 16473126

  • Jin G, LanLan Z, Li C, Dan Z. Pregnancy outcome following loop electrosurgical excision procedure (LEEP) a systematic review and meta-analysis. Arch Gynecol Obstet. 2014 Jan;289(1):85-99. doi: 10.1007/s00404-013-2955-0. Epub 2013 Jul 11.

    PubMed 23843155

  • Insinga RP, Dasbach EJ, Elbasha EH. Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model. BMC Infect Dis. 2009 Jul 29;9:119. doi: 10.1186/1471-2334-9-119.

    PubMed 19640281

  • Kocken M, Helmerhorst TJ, Berkhof J, Louwers JA, Nobbenhuis MA, Bais AG, Hogewoning CJ, Zaal A, Verheijen RH, Snijders PJ, Meijer CJ. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol. 2011 May;12(5):441-50. doi: 10.1016/S1470-2045(11)70078-X.

    PubMed 21530398

  • Conner SN, Cahill AG, Tuuli MG, Stamilio DM, Odibo AO, Roehl KA, Macones GA. Interval from loop electrosurgical excision procedure to pregnancy and pregnancy outcomes. Obstet Gynecol. 2013 Dec;122(6):1154-9. doi: 10.1097/01.AOG.0000435454.31850.79.

    PubMed 24201682

  • Spracklen CN, Harland KK, Stegmann BJ, Saftlas AF. Cervical surgery for cervical intraepithelial neoplasia and prolonged time to conception of a live birth: a case-control study. BJOG. 2013 Jul;120(8):960-5. doi: 10.1111/1471-0528.12209. Epub 2013 Mar 14.

    PubMed 23489374

  • Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, Heinze G, Stary G, Reinthaller A, Speiser P. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8.

    PubMed 22914404

  • Mathiesen O, Buus SK, Cramers M. Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study. Gynecol Oncol. 2007 Nov;107(2):219-22. doi: 10.1016/j.ygyno.2007.06.003. Epub 2007 Jul 25.

    PubMed 17655918

  • van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med. 2008 Apr 3;358(14):1465-73. doi: 10.1056/NEJMoa072685.

    PubMed 18385498

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imiquimod in people with High Grade Intraepithelial Neoplasia and Cervix Cancer, run by Barretos Cancer Hospital at 1 site in Brazil.

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 4 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 17 Feb 2021. 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 Brazil. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Efficacy of immunomodulatory treatment with Imiquimod in high grade intraepithelial lesions of the cervix compared to standard electrosurgical excision procedure (LEEP) treatment. (time frame: 30 months). 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 NCT03233412, which also lists 23 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 17 Feb 2021.

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