In this study, patients with BCC will be given neoadjuvant treatment with a drug called sonidegib. Sonidegib is a daily tablet usually given for BCC that cannot be removed by surgery or that has spread through the body. The study aims to see if sonidegib given for 12 weeks will reduce the size of tumours so surgery results in less scarring or may be avoided, with only short term topical treatment required to treat remaining tumour.
Surgery is the first line treatment for most basal cell carcinomas (BCCs) with cure rates of 88 to 96%. However, excision of large lesions in sensitive locations such as the face and scalp may result in disfigurement and impairment of function. Neoadjuvant drug treatment given before surgery aims to reduce tumour size so that surgery and recovery is easier. In this study, patients with BCC will be given neoadjuvant treatment with a drug called sonidegib. Sonidegib is a daily tablet usually given for BCC that cannot be removed by surgery or that has spread through the body. The study aims to see if sonidegib given for 12 weeks will reduce the size of tumours so surgery results in less scarring or may be avoided, with only short term topical treatment required to treat remaining tumour. This approach may also reduce the risk of recurrence. To assess response to treatment, we will use a new technology for skin tumours called optical coherence technology (OCT). This is like an ultrasound scan and is non invasive. OCT can detect the extent and nature of the tumour and build a 3D image with great accuracy. OCT will be used together with pathological analysis of tumour tissue to determine response to sonidegib.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.
Imiquimod is an immune response modifier that promotes NF-kappa-B-mediated secretion of pro-inflammatory cytokines, chemokines and other mediators. These immune responses produce cytotoxic effects that are antiproliferative and anti-tumour. Imiquimod treatment requires an extended treatment period of 6 weeks for superficial BCC. Imiquimod is an option for the treatment of small, low-risk superficial BCC when surgery, curettage or cryotherapy are inappropriate. Treatment with imiquimod will be for 5 days a week for a total of 6 weeks.
Although most BCCs are amenable to surgery, excision of large tumours in aesthetically sensitive sites may compromise function or cosmesis. Patients whose BCC has not shrunk in size or depth following 12 weeks of sonidegib will undergo surgical excision of the remaining tumour.
Patients with lesions that have progressed in size and/or depth will receive the best supportive care deemed appropriate by the treating clinician. This may be surgery, imiquimod, a clinical trial treatment, radiotherapy or any combination of these interventions
Melanoma Institute Australia
North Sydney, New South Wales, Australia
Neoadjuvant treatment response determined by optical coherence tomography
The size and spread of abnormal skin structures associated with basal cell carcinoma detected by optical coherence tomography.
Time frame: 12 weeks
Neoadjuvant treatment response determined by histopathology
The size and spread of basal cell carcinoma tumour in a biopsy taken from the known worse affected area of disease demonstrated by histopathologic analysis.
Time frame: 12 weeks
Histologic response to neoadjuvant treatment in basal cell carcinoma sub types
The amount and spread of basal cell carcinoma tumour cells and structures detected at histopathology analysis in nodular and in infiltrative sub types of BCC.
Time frame: 12 weeks
Response to neoadjuvant treatment in basal cell carcinoma sub types measured with optical coherence tomography.
The amount and spread of basal cell carcinoma tumour cells and structures detected at histopathology analysis in nodular and in infiltrative sub types of BCC.
Time frame: 12 weeks
Recurrence rate
The number of patients who have a recurrence of basal cell carcinoma at the original site of disease after having surgery or 6 weeks of topical treatment with imiquimod.
Time frame: 6 and 12 months after surgery or at the end of 6 weeks of treatment with imiquimiod.
Drug related adverse reactions
The proportion of patients experiencing any adverse drug reactions graded according to CTCAE version 4.
Time frame: 12 weeks
Discontinuation of sonidegib due to adverse reactions
The proportion of patients who discontinue sonideigb because of adverse drug reactions.
Time frame: 12 weeks
Quality of life based on SKINDEX-16
The scores obtained from the validated SKINDEX-16 quality of life questionnaire compared to baseline.
Time frame: Weeks 12 and 18 and months 6 and 12.
Patient rated cosmetic outcome after neoadjuvant treatment followed by surgery
Scores from a 3 likert scale questions assessing the patient's agreement with statements about the appearance of their surgical scar for patients who need surgery after neoadjuvant treatment.
Time frame: Week 12
Surgeon rated cosmetic outcome after neoadjuvant treatment followed by surgery
Scores from a 3 likert scale questions assessing the surgeon's agreement with statements about the appearance of their surgical scar for patients who need surgery after neoadjuvant treatment.
Time frame: Week 12
Patient rated cosmetic outcome after neoadjuvant treatment
Scores from a 3 likert scale questions assessing the patient's agreement with statements about the appearance of the remmant BCC area for patients who did not need surgery after neoadjuvant treatment.
Time frame: Week 12
Surgeon rated cosmetic outcome after neoadjuvant treatment
Scores from a 3 likert scale questions assessing the surgeons's agreement with statements about the appearance of the remmant BCC area for patients who did not need surgery after neoadjuvant treatment.
Time frame: Week 12
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