Dose-finding Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) to Treat Cervical Neoplasia

Study Overview
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Brief Summary
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An effective and safe medical therapy would be most welcome to reduce the need for surgical interventions and related adverse events and psychological impact on patients with cervical cancer precursors. In this clinical trial, the investigators propose to evaluate the efficacy and safety of photodynamic therapy (PDT) using hexaminolevulinate (HAL) for mild to moderate-grade CIN (grade 1-2).

Official Title
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A Randomized Phase II Dose-finding Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) in Patients With Low/Moderate-grade Cervical Intraepithelial Neoplasia (CIN1 or 2)

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: HAL 5% with illumination
* Drug: HAL 1% with illumination
* Drug: HAL 0.2% with illumination
* Drug: Placebo ointment without illumination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ectocervical CIN1 or CIN2 as verified by local pathology (biopsy) obtained within the last month Satisfactory colposcopy examination including: visibility of entire transformation zone including the squamocolumnar junction and visibility of entire lesion margin Negative endocervical os by colposcopy Colposcopical visible lesion at visit 2, before treatment Patients with an average sized uterine cervix (approximately 27mm diameter) suitable for application of the Klemcap Age 18 or above Written informed consent signed Exclusion Criteria: Previous treatment of CIN or invasive disease Lesion(s) extending to the vaginal vault Atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology, malignant cells on cytology or histology or other suspicion of either micro-invasive or invasive disease Suspicion of endocervical disease on colposcopy Current severe pelvic inflammatory disease, severe cervicitis, or other severe gynaecological infection as per colposcopy and clinical examination Undiagnosed vaginal bleeding History of toxic shock syndrome Known or suspected porphyria Known allergy to hexaminolevulinate or similar compounds (e.g. methyl aminolevulinate or aminolevulinic acid) Pregnancy, or intention to become pregnant during the study period Nursing Childbirth or miscarriage within six weeks of enrolment Use of heart pacemaker Participation in other clinical studies either concurrently or within the last 30 days Risk of poor protocol compliance. Patient participation should be considered with respect to living far away from the hospital, plans for moving to another city/state, frequent travelling, planning to become pregnant, drug abuse/alcoholic, difficult working hours, family obligations, other illness (e.g. psychiatric), etc. Unwillingness to use adequate birth control (not abstinence) from screening until last PDT Patient 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
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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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAL 5% with illumination<br>HAL PDT 5% | Drug: HAL 5% with illumination<br>* Treatment with a singe dose of 2g, HAL 5% ointment followed by photoactivation<br>|
| Experimental: HAL 1% with illumination<br>HAL PDT 1% | Drug: HAL 1% with illumination<br>* Treatment with a singe dose of 2g, HAL 1% ointment followed by photoactivation<br>|
| Experimental: HAL 0.2% with illumination<br>HAL PDT 0.2% | Drug: HAL 0.2% with illumination<br>* Treatment with a singe dose of 2g, HAL 0.2% ointment followed by photoactivation<br>|
| Placebo Comparator: Placebo ointment without illumination<br>Placebo without illumination | Drug: Placebo ointment without illumination<br>* Treatment with a singe dose of 2g placebo ointment, no photoactivation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Lesion Response Rates of Three Different Doses of HAL PDT and Placebo at 3 Months After Treatment. | Lesion response was defined by three variables: Histology, cytology and HPV. Patient response at three months required histology regression to CIN1 or normal, cytology of LSIL or less severe, and HPV negative. | 3 months after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of HPV Response of Three Different Doses of HAL PDT and Placebo at 3 Months After Treatment. | HPV response was defined as clearance of baseline HPV infection, asssessed by genotype | 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIN