Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02130323
Other study ID # NMCSD.2014.0040
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received April 24, 2014
Last updated June 23, 2017
Start date February 2015
Est. completion date May 9, 2017

Study information

Verified date June 2017
Source United States Naval Medical Center, San Diego
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

OBJECTIVE: The standard of care for high grade cervical intraepithelial neoplasia grade 2 to 3 (CIN 2-3) has been the excision of the cervical transformation zone by way of a loop electrosurgical excision procedure (LEEP) or cold knife conization (CKC). However, it has been recognized that these procedures can increase the risks for pre-term labor in women who still desire to conceive. Recent studies have shown that medical treatment with Imiquimod, a topical immune response modulator, has significant effects on histological regression of CIN 2-3 when compared with placebo. The investigators propose that treatment with Imiquimod may be preferable offering similar outcomes on histological regression when compared with excision or ablation while potentially avoiding or reducing the number of surgical procedure that places them at risk for future pregnancies.


Description:

MATERIALS AND METHODS: A randomized controlled trial of patients with CIN 2-3 to receive either surgical excision with LEEP or CKC versus medical therapy with Imiquimod once weekly inserted vaginally for 16 weeks. Inclusion criteria are women age 21 years or older with confirmed histological diagnosis of CIN 2-3 with a normal endocervical curettage (ECC) if obtained and satisfactory colposcopy (the transformation zone of the cervix was completely visualized.) Exclusion criteria include positive CIN2-3 on ECC, presence of cancer, pregnancy or lactation, immune deficiency, hepatitis, or hypersensitivity to Imiquimod. Patients will be randomized to receive excision with LEEP/CKC or Imiquimod 250 mg (5%) cream (12.5 mg of active ingredient) inserted vaginally once a week for 16 weeks.

The primary outcome will be histological regression to CIN 1 or less. Secondary outcomes will be complete histological regression, high-risk Human Papilloma Virus (HPV) clearance, Clearance of HPV 16, 18/45, and patient tolerance of Imiquimod regimen. Follow up with repeat pap, HPV typing to include 16 and 18/45 subtyping, and colposcopy with directed cervical biopsy will be performed at 6 months post initiation of treatment. Patients unable to complete at least 8 treatments and miss two treatments consecutively will be considered failures and offered immediate LEEP. Those patients that complete 8 treatments of Imiquimod will be reevaluated 6 months from initiating treatment. Demographic information will be obtained to include age, gravidity and parity, smoking history, and contraceptive use.

Descriptive statistics will include numbers and rates of occurrence with confidence intervals of regression, pre, and post-treatment HPV including HPV 16 and 18/45 typing, and adverse effects. The assumed regression rate for the LEEP arm varies within studies. We are choosing a conservative estimate of 85% regression rate from CIN2+ to CIN1 or less. More recently in a 2014 publication in the Journal of Virology (Author Antonio Frega, Journal of Clinical Virology 60 (2014) 39-43) 13% of the LEEP patients out of 475 had residual disease after LEEP. In this study they excluded the 10% of patients that had had positive margins on their LEEP specimen. We are not excluding them as this is intent to treat study. For Imiquimod the Grimm study found a 73.3% regression rate with those treated with the active ingredient. A non-inferiority-type design for two proportions using differences is used in which the difference between treatments is defined as medical treatment being preferable if the regression rate is not more than 15% below that of the excisional treatment. Comparison of the regression rates of the two treatments will be made by a non-inferiority Fisher's exact test.

Required sample size was assessed using the PASS software of the NCSS statistical package. Using power = 0.80 and alpha = 0.05, a power analysis predicts the need for 68 patients per arm for 136. Post-treatment HPV rates will be compared similarly. We will recruit 75 patients to each arm to buffer for a dropout rate.


Recruitment information / eligibility

Status Completed
Enrollment 22
Est. completion date May 9, 2017
Est. primary completion date December 21, 2016
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 21 Years and older
Eligibility Inclusion Criteria:

- Healthy women older than age 21, military or civilian

- Negative pregnancy test results

- Confirmed CIN 2-3 on cervical biopsy with a negative endocervical curettage (ECC) and satisfactory colposcopy visualizing the complete transformation zone of the cervix.

- The patient will be available and in the San Diego area for 6 months after enrollment to complete the clinic visits and follow up.

Exclusion Criteria:

- Positive CIN 2-3 on ECC

- Presence of cancer

- Pregnancy or lactation

- Immuno-compromised (systemic lupus erythematosus, kidney transplant)

- Hepatitis

- Hypersensitivity to Imiquimod

- Ulcerative colitis

- Crohn's disease

- Human Immunodeficiency virus

Study Design


Intervention

Drug:
Imiquimod
12.5mg (5%) once a week vaginally for 16 weeks
Procedure:
Loop Electrosurgical Excision Procedure
Patients with CIN 2-3 will be randomized to receive intervention, CKC or LEEP versus medical therapy with Imiquimod.

Locations

Country Name City State
United States Naval Medical Center San Diego San Diego California

Sponsors (1)

Lead Sponsor Collaborator
United States Naval Medical Center, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Human Papillomavirus(HPV) Clearance HPV clearance will be determined by pathology and HPV testing, followed by colposcopy.
Descriptive statistics will include numbers and rates of occurrence with confidence intervals of regression, pre and post-treatment HPV including Human Papillomavirus type 16 (HPV16) and HPV 18/45 typing, and adverse effects. A non-inferiority type design is used in which the difference between treatments is defined as medical treatment being preferable if the regression rate is not more than 10% below that of the excisional treatment. Comparison of the regression rates of the two treatments will be made by a non-inferiority Fisher's exact test.
6 months from treatment initiation
Secondary Evidence of local or systemic side effects of Imiquimod cream Patients will be seen in dysplasia clinic at Naval Medical Center San Diego (NMCSD) every 4 weeks while in treatment to determine tolerability of the Imiquimod Arm. Patients with significant symptoms will be asked to delay using Imiquimod until symptoms resolve before resuming. Patients unable to complete at least 4 weeks of treatment (1 treatment per week), will be offered immediate LEEP or surveillance at the 6 month follow up. Every 4 weeks after initiation of Imiquimod Arm for 16 weeks
Secondary Evidence of local or systemic side effects of Imiquimod cream Patients will be provided a daily phone number to a qualified nurse regarding any symptoms experienced while on the Imiquimod arm of the study. Patients will be instructed to be evaluated in the Emergency Department after clinic hours if needed for up to 6 months after study initiation. Daily after initiation of Imiquimod treatment Arm, up to 6 months after study initiation
Secondary Number of Participants with Serious and Non-Serious Adverse Events All reported Adverse Events will be captured on the Adverse Event report. Up to 6 months after study initiation
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04537156 - Efficacy, Immunogenicity and Safty Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli) Phase 3
Completed NCT02907333 - Testing Use of Condoms on Regression of Cervical Intraepithelial Neoplasia N/A
Recruiting NCT02576262 - HPV Integration Testing for Human Papillomavirus-Positive Women N/A
Completed NCT01029990 - Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program Phase 0
Recruiting NCT05078528 - Low-cost Imaging Technology for Global Prevention of Cervical Cancer N/A
Recruiting NCT05502367 - A Study of ABI-2280 Vaginal Tablet in Participants With Cervical Intraepithelial Neoplasia Phase 1/Phase 2
Completed NCT02494310 - HRME: Screening for Cervical Cancer and Its Precursors in Low‐Resource Settings N/A
Active, not recruiting NCT03429582 - Comparison of Cervical CIN II/III Treatment Outcomes With Thermal Ablation Device N/A
Active, not recruiting NCT02140021 - Biospecimen Collection and Testing for the Prevalence of Anal Dysplasia and Anal Cancer in Patients With Cervical, Vaginal and Vulvar Dysplasia and Cancer N/A
Not yet recruiting NCT05510830 - Diagnostic Cervical Conization for Persistent Infection or Integration of HPV N/A
Completed NCT02237326 - Visual Inspection With Acetic Acid Compared to Lugol's Iodine in HIV-infected Women N/A
Completed NCT00316706 - Human Papilloma Virus (HPV) Vaccine Trial in Young Adolescent Women With GlaxoSmithKline Biologicals' (GSK Bio) HPV-16/18 Vaccine Phase 3
Withdrawn NCT03143491 - Study of SOR007 Ointment for Cervical Intraepithelial Neoplasia (CIN) Phase 2
Completed NCT03293628 - Comparing Two Techniques of Haemostasis After Cervical Conization Phase 2
Recruiting NCT05266898 - Immunogenicity of Gardasil-9 HPV Vaccine in People Living With HIV Phase 4
Completed NCT02481414 - A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions Phase 2
Completed NCT02247999 - Improving Cervical Cancer Screening Among HIV-Infected Women in India
Recruiting NCT04650711 - Immunohistochemical Staining of p16 for the Screening of Cervical Cancer Phase 2
Recruiting NCT04646954 - DNA Methylation Testing for the Screening of Uterine Cervical Lesion Phase 3
Completed NCT01544478 - V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110) Phase 4