E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
sporadic superficial and nodular skin basal cell carcinomas |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042503 |
E.1.2 | Term | Superficial basal cell carcinoma |
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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 |
• To determine the safety and local tolerability of topically applied 0.75% LDE225 cream during and after 6 weeks treatment of superficial basal cell carcinomas (sBCCs) and perilesional uninvolved skin. • To assess the efficacy (clinical evaluation) of topically applied 0.75% LDE225 cream in the treatment of sBCCs during and after the 6 week treatment period. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the pharmacodynamic effect (histological signs of tumor regression; apoptosis, tumor proliferation markers) in sBCCs after treatment with topically applied 0.75% LDE225 cream. • To investigate the effect of topically applied 0.75% LDE225 cream on specific biomarkers related to the Smo pathway (Gli1, Gli2, Ptch1 and Ptch2) in sBCC tumor tissue. • To assess the LDE225 pharmacokinetics in plasma after multiple applications of 0.75% LDE225 cream onto the skin. • To evaluate the LDE225 concentration in perilesional uninvolved skin and involved skin (sBCCs) after multiple applications of 0.75% LDE225 cream onto the skin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female (non-childbearing potential) patients, ages 18 to 75 years (inclusive), with one histologically confirmed superficial or nodular basal cell carcinoma (diameter 8-20 mm), eligible for surgical excision on selected body areas (scalp, arm, frontal trunk, posterior trunk, upper legs), will be included. (Note: Presence of other non-melanoma skin cancers at sites distant from the qualifying sBCC will not a priori exclude the patient from the study). 2. Physical examination must be without significant disease findings (other than sBCC or nBCC) unless the Investigator considers an abnormality to be irrelevant to the outcome of the study. 3. At Screening, Visit 1, 15 and Safety Visit, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the supine position after the patient has rested for at least three (3) minutes and again when required after three (3) minutes in the standing position. Vital signs should be within the following ranges: oral body temperature between 35.0-37.5 C systolic blood pressure, 90-150 mm Hg diastolic blood pressure, 50-95 mm Hg pulse rate, 40 - 90 bpm If vital signs are out-of-range, the Investigator may obtain two additional readings, so that up to three (3) consecutive assessments are made, each after at least 5 minutes and with the patient seated quietly during the five (5) minutes preceding the assessment. At least the last reading must be within the ranges provided above in order for the patient to qualify. When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) associated with clinical manifestation of postural hypotension. All blood pressure measurements at other time-points should be assessed with the patient seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination. 4. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of > 40 IU/L at screening. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures (tubal ligation is not considered adequate) should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. 5. Male patients must be using two highly effective methods of contraception (comprising a barrier method such as condom or occlusive cap plus spermicide) plus ensure use by the female partner of a second method of contraception. These measures should be in place for the entire duration of the study to the Study Completion visit, males should refrain from fathering a child in the three (3) months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. 6. Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 29 kg/m2. See Appendix 3 of this protocol for BMI ranges. 7. Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. |
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E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria will be excluded from entry into or continuation in the study. 1. Previous treatment of the BCC that is selected for treatment. 2. Use of any topical treatment whether prescribed or as on OTC on the treated areas during the course of the study. 3. Any systemic treatment which is known to affect BCCs especially cytostatic treatments, retinoids and photodynamic treatments. 4. Treatment with any systemic immunomodulating drugs or systemic retinoid 4 weeks prior to initial dosing. 5. Treatment with imiquimod within 4 weeks prior to initial dosing. 6. Women of child-bearing potential; nursing or pregnant women. 7. Dark-skinned persons whose skin color prevents readily assessment of skin reactions (patients with skin phototype IV or higher (Fitzpatrick classification of Skin Phototypes (I-VI) (Pathak and Fitzpatrick 1993) will be excluded. 8. Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing. If needed, (i.e. an incidental and limited need) paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. 9. Use of any topical creams or lotions on the treated area during the course of the study. 10. A history of, or suffering from, any skin condition in the area of application. 11. Tattoos, scars or excess hair in the area of application that will prevent skin assessment. 12. A history of keloid scars. 13. Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 14. Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 15. Significant illness within two (2) weeks prior to initial dosing. 16. A past medical history of clinically significant ECG abnormalities. 17. An abnormal ECG (defined as PR > 220 msec, QRS complex > 120 msec, QTcB > 430 msec females; QTcB > 420 msec males, or any significant morphological changes, other than non-specific T-wave changes). 18. Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc). 19. History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study. 20. Laboratory safety tests outside the reference range and deemed clinically significant. 21. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 22. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 23. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. 24. Total WBC count which falls outside the range of 4000–10,000/μL, or platelets <150,000/μL at screening. 25. Patients who are exposed to UV radiation and/or tanning beds within 2 weeks before screening and during treatment. 26. Patients with history of allergy or intolerance to local anesthetics and or epinephrine to be used for skin surgical procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
see main objective section |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
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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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |