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

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.

Study Overview

• Status: Recruiting
• Conditions: Skin Cancer; Basal Cell Carcinoma; Invasive Carcinoma; Basal Cell Carcinoma of Skin, Site Unspecified
• Intervention / Treatment: Drug: Sonidegib; Drug: Imiquimod; Procedure: Surgery; Other: Best supportive care

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pascale Guitera, MD PhD; Phone Number: +61299117296; Email: pascale.guitera@melanoma.org.au

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Recruiting
      • Melanoma Institute Australia
      • Contact: Pascal Guitera, MD PhD; Phone Number: +61299117296; Email: pascale.guitera@melanoma.org.au
      • Principal Investigator: Pascale Guitera

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sonidegib followed by imiquimod; Sonidegib 200mg taken orally once a day for 12 weeks. COMPLETE OR PARTIAL RESPONSE WITH SUPERFICAL REMNANT LESION For patients with a complete response or a partial response resulting in a superficial lesion, treatment with topical imiquimod for 5 days a week for 6 weeks will be prescribed.	Drug: Sonidegib; Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.; Other Names: LDE225; Odomzo; Drug: Imiquimod; 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.; Other Names: Aldara
Experimental: Sonidegib followed by surgery; Sonidegib 200mg taken orally once a day for 12 weeks. PARTIAL RESPONSE WITH REMNANT INVASIVE LESION For patients with a no change on BCC size / depth or patients with a partial response but a remaining invasive lesion, will have surgical excscion of the remaining lesion.	Drug: Sonidegib; Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.; Other Names: LDE225; Odomzo; Procedure: Surgery; 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.; Other Names: Excision of remnant invasive basal cell carcinoma
Other: Sonidegib then best supportive care; Sonidegib 200mg taken orally once a day for 12 weeks. PROGRESSIVE DISEASE 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.	Drug: Sonidegib; Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.; Other Names: LDE225; Odomzo; Other: Best supportive care; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	12 weeks
Discontinuation of sonidegib due to adverse reactions	The proportion of patients who discontinue sonideigb because of adverse drug reactions.	12 weeks
Quality of life based on SKINDEX-16	The scores obtained from the validated SKINDEX-16 quality of life questionnaire compared to baseline.	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.	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.	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.	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.	Week 12

Collaborators and Investigators

• Sponsor: Melanoma Institute Australia
• Investigators: Study Director: Pascale Guitera, MD PhD, Melanoma Institute Australia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 13, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant; Sonidegib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: MIA2017/CT/220; HREC file number 18/087 (Other Identifier: Human Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No