Clinical trial NCT03534947: A Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Basal Cell Carcinoma
Basal Cell Carcinoma of Skin, Site Unspecified
Skin Cancer
Invasive Carcinoma
Keywords: Neoadjuvant
Sonidegib
Lead sponsor: Melanoma Institute Australia
Sponsor class: OTHER
First posted: 2018-05-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pilot study which will evaluate the efficacy and safety of short term neoadjuvant sonidegib followed by surgery or imiquimod in the management of basal cell carcinomas in cosmetically challenging locations, assessed by optical coherence tomography and histopathology. The data from this pilot study may lead to the design of larger scale trials of neoadjuvant targeted therapy with the aim to decrease the morbidity of surgical treatment and increase the probability of a curative resection in larger patient populations.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Neoadjuvant treatment response determined by optical coherence tomography
timeFrame: 12 weeks
Secondary outcomes:
measure: Neoadjuvant treatment response determined by histopathology
timeFrame: 12 weeks
measure: Histologic response to neoadjuvant treatment in basal cell carcinoma sub types
timeFrame: 12 weeks
measure: Response to neoadjuvant treatment in basal cell carcinoma sub types measured with optical coherence tomography.
timeFrame: 12 weeks
measure: Recurrence rate
timeFrame: 6 and 12 months after surgery or at the end of 6 weeks of treatment with imiquimiod.
measure: Drug related adverse reactions
timeFrame: 12 weeks
measure: Discontinuation of sonidegib due to adverse reactions
timeFrame: 12 weeks
measure: Quality of life based on SKINDEX-16
timeFrame: Weeks 12 and 18 and months 6 and 12.
measure: Patient rated cosmetic outcome after neoadjuvant treatment followed by surgery
timeFrame: Week 12
measure: Surgeon rated cosmetic outcome after neoadjuvant treatment followed by surgery
timeFrame: Week 12
measure: Patient rated cosmetic outcome after neoadjuvant treatment
timeFrame: Week 12
measure: Surgeon rated cosmetic outcome after neoadjuvant treatment
timeFrame: Week 12
Other outcomes:
Locations:
city: North Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
Study officials:
affiliation: Melanoma Institute Australia
name: Pascale Guitera, MD PhD
role: STUDY_DIRECTOR
References:
citation: Chang AL, Atwood SX, Tartar DM, Oro AE. Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced basal cell carcinoma and resistant basal carcinomas in Gorlin syndrome. JAMA Dermatol. 2013 May;149(5):639-41. doi: 10.1001/jamadermatol.2013.30. No abstract available.
citation: Cheng HM, Guitera P. Systematic review of optical coherence tomography usage in the diagnosis and management of basal cell carcinoma. Br J Dermatol. 2015 Dec;173(6):1371-80. doi: 10.1111/bjd.14042. Epub 2015 Oct 27.
citation: Cheng HM, Lo S, Scolyer R, Meekings A, Carlos G, Guitera P. Accuracy of optical coherence tomography for the diagnosis of superficial basal cell carcinoma: a prospective, consecutive, cohort study of 168 cases. Br J Dermatol. 2016 Dec;175(6):1290-1300. doi: 10.1111/bjd.14714. Epub 2016 Sep 24.
citation: Ching JA, Curtis HL, Braue JA, Kudchadkar RR, Mendoza TI, Messina JL, Cruse CW, Smith DJ Jr, Harrington MA. The impact of neoadjuvant hedgehog inhibitor therapy on the surgical treatment of extensive basal cell carcinoma. Ann Plast Surg. 2015 Jun;74 Suppl 4:S193-7. doi: 10.1097/SAP.0000000000000452.