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

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

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

Study Overview

• Status: Terminated
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Drug: Hexaminolevulinate (HAL); Drug: Hexaminolevulinate (HAL); Drug: Placebo; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Department of Obstetrics and Gyneacology, Lille University Hospital
• Germany
  • Hannover, Germany
    • Department of Obstetrics and gynecology
• Norway
  • Larvik, Norway
    • Fritzøe klinikk
  • Oslo, Norway
    • Department of Obstetrics and Gynaecology, Ullevål University Hospital
  • Trondheim, Norway
    • Medicus

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; HAL suppository (single administration, HAL 100mg), laser illumination (50J/cm2)	Drug: Hexaminolevulinate (HAL); Drug: hexaminolevulinate (HAL) Suppository HAL 100 mg for 3-7 hours application; Drug: Hexaminolevulinate (HAL); Drug: hexaminolevulinate (HAL) Ointment HAL 100 mg for 5 hours application
PLACEBO_COMPARATOR: 2; Placebo suppository (single administration), laser illumination (50J/cm2)	Drug: Placebo; Placebo suppository, for 3-7 hours application; Drug: Placebo; Placebo ointment for 5 hours application
NO_INTERVENTION: 3
ACTIVE_COMPARATOR: 4; HAL ointment (5%, 100mg, single administration), LED diode illumination (50J/cm2)	Drug: Hexaminolevulinate (HAL); Drug: hexaminolevulinate (HAL) Suppository HAL 100 mg for 3-7 hours application; Drug: Hexaminolevulinate (HAL); Drug: hexaminolevulinate (HAL) Ointment HAL 100 mg for 5 hours application
PLACEBO_COMPARATOR: 5; Placebo ointment (single administration), no illumination	Drug: Placebo; Placebo suppository, for 3-7 hours application; Drug: Placebo; Placebo ointment for 5 hours application

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

Collaborators and Investigators

• Sponsor: Photocure
• Investigators: Principal Investigator: Peter Hillemanns, MD, PhD, Medizinische Hochschule Hannover, Hannover, Germany

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (ESTIMATE): July 3, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2013
• Last Update Submitted That Met QC Criteria: April 17, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Cervical intraepithelial neoplasia (CIN)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: PC CE201/08