E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous Cell Carcinoma and Actinic Keratoses in solid organ transplant recipients |
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E.1.1.1 | Medical condition in easily understood language |
The most common fair skin cancer in solid organ transplant recipients (squamous cell carcinoma) and its preliminary stage (actinic keratoses). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000614 |
E.1.2 | Term | Actinic keratosis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
Compare efficacy of cyclic field MAL(Metvix®)-PDT versus cryotherapy in prevention of in-situ squamous cell carcinomas (de novo in-situ SCC, de novo AK) and invasive SCC at month 24. |
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E.2.2 | Secondary objectives of the trial |
At month 12: Compare efficacy of cyclic field MAL(Metvix®)-PDT versus cryotherapy in prevention de novo AK, in-situ SCC, invasive SCC. At month 12 and 24: Compare efficacy of cyclic field MAL(Metvix®)-PDT versus cryotherapy in prevention of recurrent AK, de novo AK, Basal Cell Carcinoma (BCC), de-novo SCC, and verrucae. Compare time to first invasive and in situ SCC in both groups. Compare AK lesions response rate at each visit. Compare local safety profile of cyclic field MAL(Metvix®)-PDT versus cryotherapy. Compare investigator and subject’s overall satisfaction between goups. Compare investigator’s assessment of target area cosmesis between groups.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients who are able to understand and provide written informed consent to participate in the clinical trial (signed informed consent) according to ICH-GCP • Male or nonpregnant, nonlactating female • ≥18yrs. • immunosuppressed kidney- (including simultaneous kidney/pancreas-), liver-, lung- and heart-transplanted patients • Multiple mild to moderate AK (> 5 AK) distributed over 3 target areas on the face and/or scalp (each 8x18cm2) • at least one previous invasive SCC within one of the target areas during the last 12 months before enrolment (Day 1) • Patient under stable/unchanged immunosuppressive regimen within the 6 preceding months. For patients under mTOR inhibitors, the previous SCC must have occurred while the patients were receiving a stable mTOR inhibitor therapy for at least 6 months. • Negative urine pregnancy test (the detection limit of human Choriongonadotropine (hCG) must be below 25U/ml) • Patients willing to comply with the study protocol |
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E.4 | Principal exclusion criteria |
• Patient with active invasive SCC in the target areas • Active AK grade III (Ohlsen et al.) or evidence of Bowen’s Disease (BD) in at least one target area • Known or suspected allergy or hypersensitivity to any of the trial ingredients such as methyl aminolevulinate, glyceryl monostearate, cetostearyl alcohol, poloxyl 40 stearate, methyl parahydroxy benzoate (E218), propyl parahydroxybenzoate (E216), disodium edetate, glycerol, white soft paraffin, cholesterol, isopropyl myristate, arachis oil (peanut oil), almond oil, oleyl alcohol and purified water • Patients with a porphyria • Patients with a morphoeic basal cell carcinoma within 5cm of any target area • Dermatological disease or condition that might be exacerbated by MAL(Metvix®)-PDT or cryotherapy treatment or may impair trial assessments • Evidence of unstable or uncontrolled clinically significant medical condition • Known or supposed systemic malignant tumor • Systemic chemotherapy within the last 1 year prior to randomisation • Current or previous (≤ 6 months) intake of retinoids or any other systemic treatment for AK or interferon-treatment • active topical treatment (excluding surgery) against non-melanoma skin cancer (NMSC) in at least one target area within the last 12 weeks prior to enrolment (Day 1) • Planned major change in the immunosuppression • Patients participating in a clinical trial within the last 4 weeks prior to randomisation • Female patients with childbearing potential without adequate contraception (oral contraceptive or intrauterine device during the study period and one month thereafter) • Patients who are detained or held under guard by arrangement of the law or authorities |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative incidence of SCC at month 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints • Cumulative Incidence of new AK at month 12 and 24 • Cumulative Incidence of SCC at month 12 • Cumulative Incidence of BCC at month 12 and 24 • Cumulative Incidence of Verrucae at month 12 and 24 • % of change from baseline in total AK number at each visit. • Decrease of lesions count assessed at each visit from baseline • Number of cryotherapy sessions reactively needed in reference study arm • Median time to occurrence of new AK • Median time to occurrence of new SCC
Safety Endpoints • Frequency and severity of adverse events at each visit • Local tolerability assessed by subjects: % per score 7 days after each treatment session • Pain-Score: % per score after each treatment session • Skin cosmesis: % per score at each visit
Other Endpoints • investigator and patient overall satisfaction • Cosmetic outcome |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |