Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II

Study Overview
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Brief Summary
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The investigators want to test whether treatment with a natural progesterone intravaginally increases the cure rate of cervical intraepithelial neoplasia grade I and II.

Detailed Description
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Background: The development of cervical intraepithelial neoplasia (CIN) was linked to a decreased local immune response as evidenced by a decrease of Langerhans' cell (LC) count in the cervical epithelium. Preliminary studies show that vaginally administered progesterone locally increases the number of LCs. There is no accepted treatment strategy of low grade CIN, i.e., CIN I and II, than await spontaneous regression. Thus, vaginal progesterone is expected to increase the regression rate of cervical dysplasia grade I and II. Outcome parameters: Primary outcome parameters: To evaluate whether or not a treatment with vaginal progesterone increases regression and remission rates of CIN I and II during a 6-month treatment period. Secondary outcome parameters: Change of immunohistochemically detected expression of LCs in CIN. Methods: Prospective phase II trial with vaginal progesterone as treatment of CIN I and II. 60 patients receive vaginal micronized progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16-25 for 6 months. After 3 and 6 months patients are examined for possible regression, persistence, or progression of disease and treated accordingly. Treatment of patients with progressing CIN is being discontinued after 3 months. Follow-up of patients is ensured based on current clinical practice, i.e., regular outpatient visits every 3 months, until the lesion completely regresses. Diagnosis and main inclusion criteria: CIN I and II diagnosed by punch biopsy, lesion fully visible, otherwise healthy subjects < 60 years, no history of breast cancer, patient's compliance Medication: Micronized progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16-25 Duration of treatment: 6 months

Official Title
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Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II: A Phase II Trial

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological evidence of CIN I and II Transformation zone and lesion margins fully visible Compliant subject Safe contraception Negative pregnancy test Exclusion Criteria: Lesion related CIN III, (micro)-Invasive Cancer Endocervical lesion, upper margin of lesion not visible on colposcopy Non-compliance of patient PAP V Drug related Age > 60 Hypersensitivity to progesterone or any component of the formulation Thrombophlebitis Undiagnosed vaginal bleeding Carcinoma of the breast Cerebral apoplexy Severe liver dysfunction Pregnancy Depression Diabetes Epilepsy Migraine Renal dysfunction Asthma HIV infection Hepatitis B or C Concurrent use of anticoagulants Uncontrolled hypertension (> 160/90 mmHg) Breast cancer in personal history Concurrent hormonal therapy including OC Clinical laboratory related Hemoglobin < 11 g/dl Leukocytes < 4,0 x 109/L Platelet count < 100 x 109/L Serum bilirubin > 2 x above upper cut-off value Serum GOT > 2 x above upper cut-off value Serum GPT > 2 x above upper cut-off value Serum alkaline phosphatase > 2 x above upper cut-off value Serum creatinine > 2 x above cut-off value

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: progesterone|Micronized progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16-25|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate whether or not a treatment with vaginal progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16-25 for 6 months increases regression rates of CIN I and II. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of immunohistochemically detected expression of Langerhans Cells in CIN |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical intraepithelial neoplasia (CIN), progesterone