E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Special form of skin cancer (basal cell carcinoma) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 | 10004146 |
E.1.2 | Term | Basal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004148 |
E.1.2 | Term | Basal cell carcinoma excision |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 |
Quantitative PCR will be performed to evaluate if Itraconazole leads to a significant inhibition of the Hedgehog pathway demonstrated by a significant reduction in the mRNA expression levels of GLI1, PTCH1, SMO and BCL2 in basal cell carcinomas. In addition, immunohistochemistry will be performed to analyze the changes on protein expression of GLI1, PTCH1 and SMO caused by Itrazonazole treatment. |
|
E.2.2 | Secondary objectives of the trial |
A clinical evaluable anti-tumor effect of Itraconazole will be determined as impact on BCC tumor size by imaging and clinical assessment of all lesions at study entry and prior to excision.
In order to elucidate the anti tumor effect of Itraconazole on cell level, we will determine the histopathological necrosis score on haematoxylin and eosin stained sections of all biopsies and excised basal cell carcinomas. The induction of apoptosis will be quantified immunohistochemically by staining for cleaved caspase 3. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Legally competent male and female individuals over 18 years
of age
• Patients with histopathologically confirmed BCC with a
clinical size of at least 5x5 mm after biopsy, equalling a
minimum size of 8x8 mm prior to biopsy
• Microscopically confirmed onychomycosis
• Informed consent to the study
• Patients who already take Itraconazole treating their
onychomycosis are applicable for the study if their BCC was
biopsied prior to the start of Itraconazole therapy |
|
E.4 | Principal exclusion criteria |
Individuals with nevoid basal cell carcinoma syndrome
• Prior local therapies of the BCC
• Excision planned in less than 8 or more than 14 weeks from
start of Itraconazole therapy for verum group
• Treatment with Itraconazole or other systemic antifungal
drugs within the last 2 years
• Contraindications against treatment with Itraconazole |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Inhibition of the Hedgehog pathway, represented through the reduction of the GLI1 expression |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
after collection of all samples |
|
E.5.2 | Secondary end point(s) |
A clinical evaluable anti-tumor effect of Itraconazole will be determined as impact on BCC tumor size by imaging and clinical assessment of all lesions at study entry and prior to excision.
In order to elucidate the anti tumor effect of Itraconazole on cell level, we will determine the histopathological necrosis score on haematoxylin and eosinstained sections of all biopsies and excised basal cell carcinomas. The induction of apoptosis will be quantified immunohistochemically by staining for cleaved
caspase 3. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
after collection of all samples |
|
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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 |
local therapy or no therapy |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |