A Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma

A Pilot Study to Evaluate Short Term Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinomas in Cosmetically Challenging Locations

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.

Inclusion Criteria:

• ≥18 years of age.
• Written informed consent.
• Histologically confirmed, resectable, invasive basal cell carcinoma.
• Site and size of BCC considered to be in a cosmetically challenging position for surgery.
• Patient has expressed concerns of the cosmetic outcome of surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Ability to swallow and retain oral medication.
• Anticipated life expectancy of > 12 months.
• Adequate organ function as demonstrated by blood tests.
• Willing to abstain from blood donations for 20 months from the last dose of sonidegib.
• Men with female partner of childbearing potential to use effective contraception from 14 days prior to study treatment until 6 months after the last dose.
• Female patients with active contraception or no menstrual cycle for >12 months

Exclusion Criteria:

• Inoperable basal cell carcinoma tumours.
• A concurrent cancer diagnosis requiring any systemic anti-cancer therapy.
• Serious or unstable pre-existing medical conditions or other conditions or laboratory abnormalities that could interfere with the patient's safety, consent, or compliance.
• History of malabsorption or other conditions that would interfere with the absorption of sonidegib.
• Known psychiatric or substance abuse disorders that would interfere with cooperation and compliance with the requirements of the trial.
• Prior treatment with hedgehog pathway inhibitors.
• Concomitant medications that may result in increased or decreased bioavailability of sonidegib.
• Patients with neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, rhabdomyolysis, amyotrophic lateral sclerosis and spinal muscular atrophy) due to an increased risk of muscle toxicity with sonidegib.
• Male patients expecting to father children or donate sperm during the 12 weeks of sonidegib treatment and for a further 6 months from the end of treatment.
• Pregnant or breastfeeding women