Dose-finding Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) to Treat Cervical Neoplasia
Condition: Cervical Intraepithelial Neoplasia
MeSH terms: Neoplasms; Carcinoma in Situ; Uterine Cervical Dysplasia
Intervention: HAL 5% with illumination; HAL 1% with illumination; HAL 0.2% with illumination; Placebo ointment without illumination
Intervention description: Treatment with a singe dose of 2g, HAL 5% ointment followed by photoactivation; Treatment with a singe dose of 2g, HAL 1% ointment followed by photoactivation; Treatment with a singe dose of 2g, HAL 0.2% ointment followed by photoactivation; Treatment with a singe dose of 2g placebo ointment, no photoactivation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 262.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CIN

Summary:

      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).
    

Eligibility criteria:

        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