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

Cervix Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03233412
• Other study ID #: BarretosCH-20171
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2018
• Est. completion date: January 14, 2020

Study information

• Verified date: April 2019
• Source: Barretos Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 14, 2020
• Est. primary completion date: January 14, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cervix Cancer
• High Grade Intraepithelial Neoplasia
• Neoplasms
• Uterine Cervical Neoplasms

Intervention

Procedure:
• Control
Exertion of the cervix transformation zone

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

Locations

Country	Name	City	State
Brazil	Barretos Cancer Hospital	Barretos

Sponsors (2)

Lead Sponsor	Collaborator
Barretos Cancer Hospital	Farmoquimica S.A.

Country where clinical trial is conducted

Brazil, 

References & Publications (22)

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. — View Citation

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. 2 — View Citation

Chen FP. Efficacy of imiquimod 5% cream for persistent human papillomavirus in genital intraepithelial neoplasm. Taiwan J Obstet Gynecol. 2013 Dec;52(4):475-8. doi: 10.1016/j.tjog.2013.10.004. — View Citation

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. — View Citation

Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, McCalmont T, Nayar R, Palefsky JM, Stoler MH, Wilkinson EJ, Zaino RJ, Wilbur DC; Members of LAST Project Work Groups. The Lower Anogenital Squamous Terminology Standardization Project for HPV-As — View Citation

Diaz-Arrastia C, Arany I, Robazetti SC, Dinh TV, Gatalica Z, Tyring SK, Hannigan E. Clinical and molecular responses in high-grade intraepithelial neoplasia treated with topical imiquimod 5%. Clin Cancer Res. 2001 Oct;7(10):3031-3. — View Citation

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 — View Citation

Gunderson CC, Nugent EK, Elfrink SH, Gold MA, Moore KN. A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia. Am J Obstet Gynecol. 2013 May;208(5):410.e1-6. doi: 10.1016/j.ajog.2013.01.047. Epub 2013 Feb 1. — View Citation

Haidopoulos D, Diakomanolis E, Rodolakis A, Voulgaris Z, Vlachos G, Intsaklis A. Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina? Int J Gynecol Cancer. 2005 Sep- — View Citation

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. 20 — View Citation

International Agency for Research on Cancer, World Health Organization, Globocan, Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012

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. Review. — View Citation

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 stud — View Citation

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): — View Citation

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. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2 — View Citation

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. Epub 2007 Jul 25. — View Citation

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 — View Citation

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.aj — View Citation

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. — View Citation

van Seters M, van Beurden M, de Craen AJ. Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol. 2005 May;97(2):645-51. Review. — View Citation

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 — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30 months
Secondary	Local and systemic adverse events	To assess the local and systemic adverse effects of topical immunomodulatory treatment through anamnesis and physical examination.	30 months
Secondary	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.	30 months
Secondary	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	30 months
Secondary	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.	24 months
Secondary	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.	24 months
Secondary	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.	30 months