Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) of Cervical Intraepithelial Neoplasia (CIN) Grade 1

Study Overview
=================
Brief Summary
-----------------
The study will examine the effect of HAL vs placebo photodynamic therapy of low-grade cervical precancerous lesions (dysplasia) in women.

Detailed Description
-----------------
Low-grade cervical intraepithelial neoplasia (CIN1) is caused by persistent HPV infection and may worse case develop into cancer. In most cases both the virus infection and lesions (CIN1) regress spontaneously, but must be followed up with gynecological examinations to ensure normalization. If further persistent disease and worsening to precancerous lesions (CIN2-3), the usual treatment is surgery, where one removes the tissue in the cervix where the CIN lesions are. In this research study we will evaluate a new non-surgical treatment for CIN1 using hexaminolevulinate (HAL) photodynamic therapy (PDT). HAL PDT is the combination of a medication and a specific type of light to activate the drug. HAL PDT selectively removes CIN lesions while preserving normal tissue, thus this may be an alternative to frequent gynecological consultations and local surgery that may have undesirable side effects.

Official Title
-----------------
A Randomized Phase II Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) in Patients With Low-grade Cervical Intraepithelial Neoplasia (CIN1)

Conditions
-----------------
Cervical Intraepithelial Neoplasia

Intervention / Treatment
-----------------
* Drug: Hexaminolevulinate (HAL)
* Drug: Placebo
* Drug: Hexaminolevulinate (HAL)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Satisfactory colposcopy examination Negative endocervical canal by colposcopy Ectocervical CIN1 as verified by local pathologist (biopsy). Colposcopical visible lesion at visit 2, before photoactivation Written Informed Consent signed Age 18 or above Exclusion Criteria: Previous treatment of CIN or invasive disease or suspicion of either micro-invasive or invasive disease Malignant cells on cytology or histology Atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology Suspicion of endocervical disease on colposcopy Current pelvic inflammatory disease, cervicitis, or other gynecological infection as per colposcopy and clinical examination Known or suspected porphyria Known allergy to hexaminolevulinate or similar compounds (e.g. methyl aminolevulinate or aminolevulinic acid) Use of heart pacemaker Pregnancy Nursing Childbirth or miscarriage within six weeks of enrolment - Known Participation in other competitive clinical studies either concurrently or within the last 30 days Risk of poor protocol compliance Not willing to use adequate birth control from screening until last PDT Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>HAL suppository (single administration, HAL 100mg), laser illumination (50J/cm2) | Drug: Hexaminolevulinate (HAL)<br>* Drug: hexaminolevulinate (HAL) Suppository HAL 100 mg for 3-7 hours application<br>|
| Placebo Comparator: 2<br>Placebo suppository (single administration), laser illumination (50J/cm2) | Drug: Placebo<br>* Placebo suppository, for 3-7 hours application<br>|
| No Intervention: 3<br> | |
| Active Comparator: 4<br>HAL ointment (5%, 100mg, single administration), LED diode illumination (50J/cm2) | Drug: Hexaminolevulinate (HAL)<br>* Drug: hexaminolevulinate (HAL) Ointment HAL 100 mg for 5 hours application<br>|
| Placebo Comparator: 5<br>Placebo ointment (single administration), no illumination | Drug: Placebo<br>* Placebo ointment for 5 hours application<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Based on histology, cytology and HPV status. Complete response is defined as normal pathology, normal cytology and negative HPV. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication of HPV | High risk HPV | 6 months | 
| Incidence of Patients With Adverse Events |  | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cervical intraepithelial neoplasia (CIN)