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

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)

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).

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Drug: HAL 5% with illumination; Drug: HAL 1% with illumination; Drug: HAL 0.2% with illumination; Drug: Placebo ointment without illumination

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany
    • University Hospital Hannover
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Photocure
• Investigators: Principal Investigator: Peter Hillemanns, MD, PhD, University Hospital Hannover

Publications and helpful links

General Publications

• Hillemanns P, Garcia F, Petry KU, Dvorak V, Sadovsky O, Iversen OE, Einstein MH. A randomized study of hexaminolevulinate photodynamic therapy in patients with cervical intraepithelial neoplasia 1/2. Am J Obstet Gynecol. 2015 Apr;212(4):465.e1-7. doi: 10.1016/j.ajog.2014.10.1107. Epub 2014 Oct 31.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 7, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 8, 2010

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: April 8, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: CIN
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: PC CE203/10