E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vulval Intraepithelial Neoplasia grade 3 (VIN 3) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057313 |
E.1.2 | Term | Vulval intraepithelial neoplasia grade III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether there is evidence that either (or both) of the topical treatments are active, safe and feasible to use, and would therefore warrant further investigation in a phase III setting. |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
T-VIN: Collection and storage of tissue and blood samples from patients with vulval intraepithelial neoplasia receiving topical treatment, for future translational research. |
|
E.3 | Principal inclusion criteria |
1. Female ≥16 years
2. Biopsy proven VIN 3 (including visible peri-anal disease not extending into the anal canal), biopsy to have been taken within the last three months
3. At least one lesion that can be accurately measured (using RECIST criteria) in at least one dimension with longest diameter ≥ 20mm OR in two perpendicular dimensions that when multiplied together give a surface area of greater than 120mm squared
4. Using a reliable method of contraception (excluding condoms) if sexually active
5 Written informed consent to participate in trial. |
|
E.4 | Principal exclusion criteria |
1. Any patient with impaired renal function (defined as serum creatinine> 133 µmol/l or > 1.5 mg/dl)
2. Any patient with current anogenital carcinoma or any patient who, in the PIs opinion, is at a high risk of developing invasive disease (patients in whom invasive disease or microinvasive disease is suspected should have adequate biopsies to exclude this prior to entry)
3. Pregnant, breast feeding or trying to conceive
4. Active treatment for VIN within the previous four weeks
5. Known allergy to either of the topical treatments or any components in either cream
6. Unable to comply with protocol treatment
7. Previous failure of imiquimod or cidofovir following treatment three times a week for a minimum of 12 weeks.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is histologically confirmed complete response (clear of lesion) by 30 weeks. The assessment of response will consist of the use of RECIST criteria and a histological confirmation from the site of the lesion. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 weeks after the start of treatment |
|
E.5.2 | Secondary end point(s) |
1.Toxicities
2.Concordance
3.HPV presence, HPV type, HPV integration status
4.Recurrence rate at two years (in complete responders only) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Toxicities collected throughout study
2. Concorance monitored thoughout the study
3. Evaluated at the end of the study when all translational samples have been collected
4. Approximately two years after the last randomised patient to show a complete response |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
A Fleming’s single stage design will be applied to each of the arms |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will be considered closed when the last patient has completed protocol treatment and received their biopsy six weeks later (including cross over treatment). However, further observational follow up of all patients who have had a complete response will continue for a maximum of two years. Patients who have not had a complete response will be returned to normal clinical follow up. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |