Efficacy and Safety Trial of Topical Resiquimod Gel (0.06%) in Patients With Nodular Basal Cell Carcinoma

Study Overview
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Brief Summary
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The primary objective is the observation and description of the preliminary efficacy of resiquimod gel 0.06% on a single nodular basal cell carcinoma (nBCC) in a small group of patients.

Detailed Description
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efficacy assessments: Histopathological findings based on the biopsies of the primary tumor location and the tissue excision at the end of trial (histological cure). Description of the clinical-therapeutic effect of resiquimod on nBCC (nodular-basal cell carcinoma) by visual inspection (clinical evaluation of treatment area and assessment of complete clinical clearance) RNA-analysis (analysis of gene expressions for cytokines, cytotoxic and apoptotic signals) Investigator's global judgment of efficacy by means of a 7-point scale Safety assessments: Evaluation of Adverse Events (AEs) and Serious Adverse Events (SAEs) Evaluation of local tolerability (local skin reactions as erythema, edema, erosion/ulceration, exsudate, dryness, encrustation) by means of symptom scoring scales (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = very severe). Evaluation of systemic tolerability [hematology (erythrocytes, leucocytes including neutrophils, hemoglobin, hematocrit, thrombocytes), blood chemistry (alkaline phosphatase, bilirubin, aspartate transaminase (ASAT), alanine transaminase (ALAT), serum creatinine), vital signs]. The thresholds concerning laboratory abnormalities that determine patient's discontinuation from trial were predefined upfront. Evaluation of the number of patients withdrawn from the trial Investigator's global judgment of tolerability by means of a 6-point scale Photographic documentation of the treatment area Exploratory parameter: C-reactive protein (CRP) Interferon-alpha, interleukin-6, interleukin-12, interferon-gamma, TNF-alpha (up-regulation of gene expression) Immunohistochemistry and characterization of cell types (CD8, T-cells, macrophages, dendritic cells) In addition, blood serum samples will be preserved and frozen for later tests that will be specified to the patients. The preserved material will be stored for a maximum of 2 years.

Official Title
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Bi-center, Open Label, Non-comparative Trial Exploring Efficacy and Safety of Topical Resiquimod Gel (0.06%) in Patients With Nodular Basal Cell Carcinoma (nBCC)

Conditions
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Nodular Basal Cell Carcinoma

Intervention / Treatment
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* Drug: 0.06% Resiquimod Gel - A
* Drug: 0.06% Resiquimod Gel - B
* Drug: 0.06% Resiquimod Gel - C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed consent form. Male or non-pregnant, non-lactating female, ≥ 18 years. Must have a previously untreated, histologically confirmed nBCC on head, neck, trunk or arms. nBCC must not be larger than 20 mm in diameter and must be less than 5 mm in depth. Willing and able to participate in the trial as an outpatient and comply with all trial requirements. Exclusion Criteria: nBCC located close to or at mouth or eyes. Patients who have had an organ transplant. Known autoimmune disorder (especially psoriasis), impaired immune system (e.g. HIV), known thyroid abnormalities, known depression. An open wound or an infection in treatment area. Dermatological disease or condition (e.g. rosacea, atopic dermatitis, eczema) in the treatment or surrounding area that might impair trial assessments. Evidence of an active infection or systemic cancer. Flu or flu-like symptoms (including general indisposition, fever, nausea, muscle pain, chills) within a week before start of the trial. Known allergy or hypersensitivity to any of the trial gel ingredients. Evidence of unstable or uncontrolled clinically significant medical conditions as determined by the investigator (e.g., renal or hepatic disease). Current alcohol abuse or chemical dependency as assessed by the investigator. Patient who is detained or committed to an institution by a law court or by legal authorities. Participation in another clinical trial within one month before start of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.06% Resiquimod Gel - A<br>60 mg gel Once daily prior to normal sleeping hours 5x within 1 week (Monday to Friday) for 4 weeks (at maximum) or until clinical manifestation of skin erosion/crust formation | Drug: 0.06% Resiquimod Gel - A<br>* single 60mg dose<br>* Other names: CD11301;|
| Experimental: 0.06% Resiquimod Gel - B<br>100 mg gel Once daily prior to normal sleeping hours 5x within 1 week (Monday to Friday) for 4 weeks (at maximum) or until clinical manifestation of skin erosion/crust formation | Drug: 0.06% Resiquimod Gel - B<br>* single 100mg dose<br>* Other names: CD11301;|
| Experimental: 0.06% Resiquimod Gel - C<br>100 mg gel Once daily prior to normal sleeping hours 5x within 1 week (Monday to Friday) for 4 weeks (at maximum) or until clinical manifestation of skin erosion/crust formation The BCC will be pretreated. A shave biopsy (curettage or scraping off the tissue in a broad, superficial, tangential way) will be performed | Drug: 0.06% Resiquimod Gel - C<br>* shave biopsy of BCC followed by single 100mg dose<br>* Other names: CD11301;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Cure Rate |  | 8 weeks after a maximal treatment period of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clinical Clearance Rate |  | 8 weeks after the 4 weeks treatment period | 
| Evaluation of Local Tolerability by Means of 5-point Scales | local skin reactions as erythema, edema, erosion/ulceration, exudate, dryness, encrustation judged by investigator by means of 5-point scales (0 = absent, 1 = slight, 2 = moderate, 3 = severe, 4 = very severe). | up to 12 weeks | 
| Evaluation of Systemic Tolerability Based on Haematology and Blood Chemistry Values and Vital Signs |  | up to 12 weeks | 
| Global Judgment of Tolerability by Investigator by Means of a 6-point Scale |  | 8 weeks after a maximal treatment period of 4 weeks |