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

NCT03534947 | Completed Phase 2

• 2 other identifiers: MIA2017/CT/220HREC file number 18/087
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Basal Cell Carcinoma; Basal Cell Carcinoma of Skin, Site Unspecified; Skin Cancer; Invasive Carcinoma

Keywords

Neoadjuvant; Sonidegib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Neoadjuvant treatment response determined by histopathology

  12 weeks

• Histologic response to neoadjuvant treatment in basal cell carcinoma sub types

  12 weeks

• Response to neoadjuvant treatment in basal cell carcinoma sub types measured with optical coherence tomography.

  12 weeks

• Recurrence rate

  6 and 12 months after surgery or at the end of 6 weeks of treatment with imiquimiod.

• Drug related adverse reactions

  12 weeks

Study Arms (3)

Sonidegib followed by imiquimod

EXPERIMENTAL

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; Drug: Imiquimod

Sonidegib followed by surgery

EXPERIMENTAL

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; Procedure: Surgery

Sonidegib then best supportive care

OTHER

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; Other: Best supportive care

Interventions

Sonidegib DRUG

Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.

Also known as: LDE225, Odomzo

Sonidegib followed by imiquimod; Sonidegib followed by surgery; Sonidegib then best supportive care

Imiquimod DRUG

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.

Also known as: Aldara

Sonidegib followed by imiquimod

Surgery PROCEDURE

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.

Also known as: Excision of remnant invasive basal cell carcinoma

Sonidegib followed by surgery

Best supportive care OTHER

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

Sonidegib then best supportive care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• 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

Sponsors & Collaborators

• Melanoma Institute Australia: lead

Study Sites (1)

Melanoma Institute Australia

North Sydney, New South Wales, 2060, Australia

Location

Related Publications (4)

• 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.

  PMID: 23677114 BACKGROUND

• 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.

  PMID: 26211438 BACKGROUND

• 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.

  PMID: 27146027 BACKGROUND

• 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.

  PMID: 25695449 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Basal Cell; Skin Neoplasms

Interventions

sonidegib; Imiquimod; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pascale Guitera, MD PhD

  Melanoma Institute Australia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: May 23, 2018
• Study Start: July 23, 2019
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

AU (1)