Imiquimod in Preventing Cervical Cancer in Women With Cervical Neoplasia

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain substances to try to prevent the development of cancer. Applying topical imiquimod before abnormal cervical cells are removed may be effective in preventing cervical cancer. PURPOSE: Randomized phase II trial to study the effectiveness of applying topical imiquimod before abnormal cervical cells are removed in preventing cervical cancer in patients who have recurrent or persistent cervical neoplasia.

Detailed Description
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OBJECTIVES: Compare the chemopreventive efficacy of topical imiquimod followed by local ablative or excisional therapy vs ablative/excisional therapy alone in patients with recurrent or high-grade cervical intraepithelial neoplasia. Compare the toxicity of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Determine the safety and tolerability of imiquimod in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease (primary vs recurrent or persistent), severity of dysplasia (grade I vs grade II vs grade III), current tobacco use (yes vs no), planned surgical procedure (excisional vs laser vs cryotherapy vs other), and time since first abnormal Pap smear, including pathology of ascus favor dysplasia (less than 1 year vs 1-3 years vs more than 3 years). Patients are randomized to one of two treatment arms. Arm I: Patients undergo ablative or excisional therapy. Arm II: Patients have topical imiquimod applied to the cervix for 6-10 hours twice weekly for a total of 5 doses. Within 3-4 weeks after the final application, patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, after last dose of study drug (arm II only), 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy. PROJECTED ACCRUAL: A total of 66-152 (33-76 per treatment arm) will be accrued for this study within 18 months.

Official Title
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Phase II Topical Immunomodulatory Therapy With Imiquimod for the Chemoprevention of Recurrent and High-Grade Cervical Intraepithelial Neoplasia (CIN)

Conditions
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Cervical Cancer, Precancerous Condition

Intervention / Treatment
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* Drug: imiquimod
* Procedure: Ablative or excisional therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary grade II or III cervical intraepithelial neoplasia (CIN) or persistent grade I-III CIN (dysplasia that is not new and requires treatment) Squamous cell lesions not involving endocervix by colposcopy OR colposcopy with negative cytobrush or endocervical curettage No untreated cervical or vaginal infection other than human papilloma virus No desire for hysterectomy as ablative therapy PATIENT CHARACTERISTICS: Age: 18 and over Life expectancy: At least 5 years Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study HIV negative No AIDS No known hypersensitivity to imiquimod No latex allergy PRIOR CONCURRENT THERAPY: Other: No concurrent immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ablative or excisional therapy<br>Patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy. | Procedure: Ablative or excisional therapy<br> <br> |
| Experimental: Ablative or excisional therapy + imiquimod<br>Patients have topical imiquimod applied to the cervix for 6-10 hours twice weekly for a total of 5 doses. Within 3-4 weeks after the final application, patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, after last dose of study drug, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy. | Drug: imiquimod<br> <br> Procedure: Ablative or excisional therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Up to 7.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the quality of life of patients treated with these regimens |  | Up to 7.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, cervical intraepithelial neoplasia grade 1, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3