Cervical Intraepithelial Neoplasia
Conditions
Keywords
Cervical intraepithelial neoplasia (CIN)
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.
Interventions
Drug: hexaminolevulinate (HAL) Suppository HAL 100 mg for 3-7 hours application
DRUGPlacebo
Placebo suppository, for 3-7 hours application
Sponsors
Photocure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | 6 month | Based on histology, cytology and HPV status. Complete response is defined as normal pathology, normal cytology and negative HPV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eradication of HPV | 6 months | High risk HPV |
| Incidence of Patients With Adverse Events | 3 months | — |
Countries
France, Germany, Norway
Participant flow
Recruitment details
All subjects recruited from medical clinics/hospitals. Start of recruitment arms 1-3: Jan 2009 End of recruitment arms 1-3: Feb 2010 Start of recruitment arms 4-5: Nov 2010 End of recruitment arms 4-5: Jul 2011
Pre-assignment details
Recruitment to part 1, including arms 1-3, completed before initiation of part 2 (arms 4-5). Arms 4 and 5 was a protocol amendment.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: HAL Suppository, Laser Illumination | 47 |
| Arm 2: Placebo Suppository, Laser Illumination | 12 |
| Arm 3: No Intervention | 11 |
| Arm 4: HAL Ointment, LED Diode Illumination | 10 |
| Arm 5: Placebo Ointment, no Illumination | 3 |
| Total | 83 |
Baseline characteristics
| Characteristic | Arm 1: HAL Suppository, Laser Illumination | Arm 2: Placebo Suppository, Laser Illumination | Arm 3: No Intervention | Arm 4: HAL Ointment, LED Diode Illumination | Arm 5: Placebo Ointment, no Illumination | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 12 Participants | 11 Participants | 10 Participants | 3 Participants | 83 Participants |
| Age Continuous | 30.2 years STANDARD_DEVIATION 6.9 | 29.1 years STANDARD_DEVIATION 4.7 | 32.5 years STANDARD_DEVIATION 8.4 | 38.8 years STANDARD_DEVIATION 9.4 | 31.0 years STANDARD_DEVIATION 4 | 31.4 years STANDARD_DEVIATION 7.1 |
| Region of Enrollment France | 7 participants | 1 participants | 1 participants | 1 participants | 0 participants | 10 participants |
| Region of Enrollment Germany | 40 participants | 10 participants | 10 participants | 0 participants | 0 participants | 60 participants |
| Region of Enrollment Norway | 0 participants | 1 participants | 0 participants | 9 participants | 3 participants | 13 participants |
| Sex: Female, Male Female | 47 Participants | 12 Participants | 11 Participants | 10 Participants | 3 Participants | 83 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 47 | 3 / 12 | 1 / 11 | 6 / 10 | 2 / 3 |
| serious Total, serious adverse events | 3 / 47 | 0 / 12 | 1 / 11 | 0 / 10 | 0 / 3 |
Outcome results
Primary
Complete Response Rate
Based on histology, cytology and HPV status. Complete response is defined as normal pathology, normal cytology and negative HPV.
Time frame: 6 month
Population: Per protocol population. Patients with major protocol violations excluded.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Arm 1: HAL Suppository, Laser Illumination | Complete Response Rate | 57.1 percentage of no. of patients analyzed | 0 |
| Arm 2: Placebo Suppository, Laser Illumination | Complete Response Rate | 40.0 percentage of no. of patients analyzed | 0 |
| Arm 3: No Intervention | Complete Response Rate | 0.0 percentage of no. of patients analyzed | 0 |
| Arm 4: HAL Ointment, LED Diode Illumination | Complete Response Rate | 90.0 percentage of no. of patients analyzed | 0 |
| Arm 5: Placebo Ointment, no Illumination | Complete Response Rate | 33.3 percentage of no. of patients analyzed | 0 |
Secondary
Eradication of HPV
High risk HPV
Time frame: 6 months
Population: Patients who were positive for high risk HPV at baseline
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Arm 1: HAL Suppository, Laser Illumination | Eradication of HPV | 60.0 percentage of no. of patients analyzed | 0 |
| Arm 2: Placebo Suppository, Laser Illumination | Eradication of HPV | 28.6 percentage of no. of patients analyzed | 0 |
| Arm 3: No Intervention | Eradication of HPV | 100 percentage of no. of patients analyzed | 0 |
| Arm 4: HAL Ointment, LED Diode Illumination | Eradication of HPV | 50.0 percentage of no. of patients analyzed | 0 |
| Arm 5: Placebo Ointment, no Illumination | Eradication of HPV | 33.3 percentage of no. of patients analyzed | 0 |
Secondary
Incidence of Patients With Adverse Events
Time frame: 3 months
Population: All patients treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: HAL Suppository, Laser Illumination | Incidence of Patients With Adverse Events | 44.7 percentage of no of patients analyzed |
| Arm 2: Placebo Suppository, Laser Illumination | Incidence of Patients With Adverse Events | 25.0 percentage of no of patients analyzed |
| Arm 3: No Intervention | Incidence of Patients With Adverse Events | 18.2 percentage of no of patients analyzed |
| Arm 4: HAL Ointment, LED Diode Illumination | Incidence of Patients With Adverse Events | 70.0 percentage of no of patients analyzed |
| Arm 5: Placebo Ointment, no Illumination | Incidence of Patients With Adverse Events | 66.7 percentage of no of patients analyzed |