NCT02669459

Brief Summary

The purpose of this study is to investigate if imiquimod can be used as a non-invasive option in the treatment of residual/recurrent CIN lesions.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
433

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started May 2016

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 15, 2016

Completed
17 days until next milestone

First Posted

Study publicly available on registry

February 1, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

May 1, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2020

Completed
Last Updated

February 6, 2018

Status Verified

February 1, 2018

Enrollment Period

2.8 years

First QC Date

January 15, 2016

Last Update Submit

February 5, 2018

Conditions

Cervical Intraepithelial Neoplasia

Keywords

Cervical Intraepithelial NeoplasiaImiquimodHuman papillomavirusquality of lifebiological markers

Outcome Measures

Primary Outcomes (1)

  • Reduction to normal cytology

    6 months after treatment

Secondary Outcomes (8)

  • Reduction to no dysplasia

    10 weeks after the treatment

  • presence or absence of HPV DNA in CIN lesions

    presence in biopsy before start treatment, cervical smear 6 months after treatment

  • tolerability to the treatment/side effects

    At 6 months, worst grade observed.

  • tolerability to the treatment/side effects

    At 6 months, worst grade observed.

  • quality of life

    at inclusion for study, 6 and 12 months after start treatment

  • +3 more secondary outcomes

Study Arms (2)

LLETZ

ACTIVE COMPARATOR

LLETZ (Large Loop excision of the transformation zone) treatment conform current guidelines, which is also the current gold standard in the Netherlands

Procedure: LLETZ

Imiquimod 5% cream

OTHER

intervention group

Drug: Imiquimod

Interventions

ImiquimodDRUG

12,5 mg imiquimod three times per week during 16 weeks

Also known as: aldara
Imiquimod 5% cream
LLETZPROCEDURE

surgical treatment for CIN, current gold standard

Also known as: Large Loop Excision of the transformation zone
LLETZ

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically proven CIN 2 or CIN 3, without invasion after previous surgical treatment at least 6 months before diagnosis.
  • Histologically proven recurrent CIN 1 after previous surgical treatment at least 6 months before diagnosis. Persistent CIN 1 is defined as CIN 1 at least persistent for 6 months and proven with histology.
  • The patient is willing to use a medically acceptable method of contraception throughout the study
  • Women older than 18 years of age.

You may not qualify if:

  • Pregnancy or lactation
  • (Micro-)invasive carcinoma
  • Past history of cervical cancer
  • Hypersensitivity of any components of the formulation
  • History of psoriasis or other inflammatory dermatosis of the vulva
  • Immunodeficiency or treatment with immunosuppressive medication
  • Insufficient understanding of the Dutch or English language

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Erasmus Medical center

Rotterdam, South Holland, 3015 CE, Netherlands

RECRUITING

Related Publications (24)

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    PMID: 25220842RESULT

  • Wright TC Jr, Gagnon S, Richart RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol. 1992 Feb;79(2):173-8.

    PMID: 1731281RESULT

  • Martin-Hirsch PL, Paraskevaidis E, Kitchener H. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2000;(2):CD001318. doi: 10.1002/14651858.CD001318.

    PMID: 10796771RESULT

  • Luesley DM, McCrum A, Terry PB, Wade-Evans T, Nicholson HO, Mylotte MJ, Emens JM, Jordan JA. Complications of cone biopsy related to the dimensions of the cone and the influence of prior colposcopic assessment. Br J Obstet Gynaecol. 1985 Feb;92(2):158-64. doi: 10.1111/j.1471-0528.1985.tb01068.x.

    PMID: 3970895RESULT

  • Sadek AL. Needle excision of the transformation zone: A new method for treatment of cervical intraepithelial neoplasia. Am J Obstet Gynecol. 2000 Apr;182(4):866-71. doi: 10.1016/s0002-9378(00)70337-1.

    PMID: 10764464RESULT

  • 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.

    PMID: 24201682RESULT

  • 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.

    PMID: 23843155RESULT

  • Bevis KS, Biggio JR. Cervical conization and the risk of preterm delivery. Am J Obstet Gynecol. 2011 Jul;205(1):19-27. doi: 10.1016/j.ajog.2011.01.003. Epub 2011 Feb 23.

    PMID: 21345402RESULT

  • Ortoft G, Henriksen T, Hansen E, Petersen L. After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy. BJOG. 2010 Feb;117(3):258-67. doi: 10.1111/j.1471-0528.2009.02438.x. Epub 2009 Nov 26.

    PMID: 19943823RESULT

  • 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.

    PMID: 23489374RESULT

  • Serati M, Siesto G, Carollo S, Formenti G, Riva C, Cromi A, Ghezzi F. Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study. Eur J Obstet Gynecol Reprod Biol. 2012 Nov;165(1):86-90. doi: 10.1016/j.ejogrb.2012.06.026. Epub 2012 Jul 6.

    PMID: 22771223RESULT

  • Rebolj M, Helmerhorst T, Habbema D, Looman C, Boer R, van Rosmalen J, van Ballegooijen M. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia: population based cohort study. BMJ. 2012 Oct 31;345:e6855. doi: 10.1136/bmj.e6855.

    PMID: 23117059RESULT

  • Strander B, Andersson-Ellstrom A, Milsom I, Sparen P. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ. 2007 Nov 24;335(7629):1077. doi: 10.1136/bmj.39363.471806.BE. Epub 2007 Oct 24.

    PMID: 17959735RESULT

  • McIndoe WA, McLean MR, Jones RW, Mullins PR. The invasive potential of carcinoma in situ of the cervix. Obstet Gynecol. 1984 Oct;64(4):451-8.

    PMID: 6483293RESULT

  • Ryu A, Nam K, Kwak J, Kim J, Jeon S. Early human papillomavirus testing predicts residual/recurrent disease after LEEP. J Gynecol Oncol. 2012 Oct;23(4):217-25. doi: 10.3802/jgo.2012.23.4.217. Epub 2012 Sep 19.

    PMID: 23094124RESULT

  • Cubie HA, Canham M, Moore C, Pedraza J, Graham C, Cuschieri K. Evaluation of commercial HPV assays in the context of post-treatment follow-up: Scottish Test of Cure Study (STOCS-H). J Clin Pathol. 2014 Jun;67(6):458-63. doi: 10.1136/jclinpath-2013-202014. Epub 2014 Jan 16.

    PMID: 24436334RESULT

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. doi: 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F.

    PMID: 10451482RESULT

  • de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, de Ruiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GA, Lombardi LE, Banjo A, Menendez C, Domingo EJ, Velasco J, Nessa A, Chichareon SC, Qiao YL, Lerma E, Garland SM, Sasagawa T, Ferrera A, Hammouda D, Mariani L, Pelayo A, Steiner I, Oliva E, Meijer CJ, Al-Jassar WF, Cruz E, Wright TC, Puras A, Llave CL, Tzardi M, Agorastos T, Garcia-Barriola V, Clavel C, Ordi J, Andujar M, Castellsague X, Sanchez GI, Nowakowski AM, Bornstein J, Munoz N, Bosch FX; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.

    PMID: 20952254RESULT

  • Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, Voorhorst FJ, Verheijen RH, van Groningen K, Boon ME, Ruitinga W, van Ballegooijen M, Snijders PJ, Meijer CJ. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet. 2007 Nov 24;370(9601):1764-72. doi: 10.1016/S0140-6736(07)61450-0. Epub 2007 Oct 4.

    PMID: 17919718RESULT

  • Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012 Jan;13(1):78-88. doi: 10.1016/S1470-2045(11)70296-0. Epub 2011 Dec 14.

    PMID: 22177579RESULT

  • Moore EE, Danielewski JA, Garland SM, Tan J, Quinn MA, Stevens MP, Tabrizi SN. Clearance of human papillomavirus in women treated for cervical dysplasia. Obstet Gynecol. 2011 Jan;117(1):101-108. doi: 10.1097/AOG.0b013e3182020704.

    PMID: 21173650RESULT

  • Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009 Jul 25;374(9686):301-14. doi: 10.1016/S0140-6736(09)61248-4. Epub 2009 Jul 6.

    PMID: 19586656RESULT

  • 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.

    PMID: 22914404RESULT

  • van de Sande AJM, Koeneman MM, Gerestein CG, Kruse AJ, van Kemenade FJ, van Beekhuizen HJ. TOPical Imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia (TOPIC-2 trial): a study protocol for a randomized controlled trial. BMC Cancer. 2018 Jun 15;18(1):655. doi: 10.1186/s12885-018-4510-7.

    PMID: 29902979DERIVED

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Precancerous ConditionsNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Intervention Hierarchy (Ancestors)

AminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Heleen van beekhuizen, MD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Meike van de Sande, MD

CONTACT

0031-6-22196507a.vandesande@erasmusmc.nl

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
A. van de Sande, MD

Study Record Dates

First Submitted

January 15, 2016

First Posted

February 1, 2016

Study Start

May 1, 2016

Primary Completion

March 1, 2019

Study Completion

March 1, 2020

Last Updated

February 6, 2018

Record last verified: 2018-02

Locations

NL(1)