Back to resultsA Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma (SONIB)
Primary Purpose
Basal Cell Carcinoma, Basal Cell Carcinoma of Skin, Site Unspecified, Skin Cancer
Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Sonidegib
Imiquimod
Surgery
Best supportive care
Sponsored by
About this trial
This is an interventional treatment trial for Basal Cell Carcinoma focused on measuring Neoadjuvant, 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
Sites / Locations
- Melanoma Institute AustraliaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Other
Arm Label
Sonidegib followed by imiquimod
Sonidegib followed by surgery
Sonidegib then best supportive care
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Drug related adverse reactions
The proportion of patients experiencing any adverse drug reactions graded according to CTCAE version 4.
Discontinuation of sonidegib due to adverse reactions
The proportion of patients who discontinue sonideigb because of adverse drug reactions.
Quality of life based on SKINDEX-16
The scores obtained from the validated SKINDEX-16 quality of life questionnaire compared to baseline.
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.
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.
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.
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.
Full Information
NCT ID
NCT03534947
First Posted
May 1, 2018
Last Updated
March 15, 2023
Sponsor
Melanoma Institute Australia
1. Study Identification
Unique Protocol Identification Number
NCT03534947
Brief Title
A Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma
Acronym
SONIB
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 23, 2019 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Melanoma Institute Australia
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma, Basal Cell Carcinoma of Skin, Site Unspecified, Skin Cancer, Invasive Carcinoma
Keywords
Neoadjuvant, Sonidegib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sonidegib followed by imiquimod
Arm Type
Experimental
Arm Description
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.
Arm Title
Sonidegib followed by surgery
Arm Type
Experimental
Arm Description
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.
Arm Title
Sonidegib then best supportive care
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sonidegib
Other Intervention Name(s)
LDE225, Odomzo
Intervention Description
Sonidegib is a selective and orally bioavailable Smoothened (Smo) antagonist. The dose will be 200mg taken once a day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Imiquimod
Other Intervention Name(s)
Aldara
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Surgery
Other Intervention Name(s)
Excision of remnant invasive basal cell carcinoma
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Best supportive care
Intervention Description
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
Primary Outcome Measure Information:
Title
Neoadjuvant treatment response determined by optical coherence tomography
Description
The size and spread of abnormal skin structures associated with basal cell carcinoma detected by optical coherence tomography.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Neoadjuvant treatment response determined by histopathology
Description
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
Title
Histologic response to neoadjuvant treatment in basal cell carcinoma sub types
Description
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
Title
Response to neoadjuvant treatment in basal cell carcinoma sub types measured with optical coherence tomography.
Description
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
Title
Recurrence rate
Description
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.
Title
Drug related adverse reactions
Description
The proportion of patients experiencing any adverse drug reactions graded according to CTCAE version 4.
Time Frame
12 weeks
Title
Discontinuation of sonidegib due to adverse reactions
Description
The proportion of patients who discontinue sonideigb because of adverse drug reactions.
Time Frame
12 weeks
Title
Quality of life based on SKINDEX-16
Description
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.
Title
Patient rated cosmetic outcome after neoadjuvant treatment followed by surgery
Description
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
Title
Surgeon rated cosmetic outcome after neoadjuvant treatment followed by surgery
Description
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
Title
Patient rated cosmetic outcome after neoadjuvant treatment
Description
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
Title
Surgeon rated cosmetic outcome after neoadjuvant treatment
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pascale Guitera, MD PhD
Phone
+61299117296
Email
pascale.guitera@melanoma.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pascale Guitera, MD PhD
Organizational Affiliation
Melanoma Institute Australia
Official's Role
Study Director
Facility Information:
Facility Name
Melanoma Institute Australia
City
North Sydney
State/Province
New South Wales
ZIP/Postal Code
2060
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pascal Guitera, MD PhD
Phone
+61299117296
Email
pascale.guitera@melanoma.org.au
First Name & Middle Initial & Last Name & Degree
Pascale Guitera
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23677114
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.
Results Reference
background
PubMed Identifier
26211438
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.
Results Reference
background
PubMed Identifier
27146027
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.
Results Reference
background
PubMed Identifier
25695449
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.
Results Reference
background
Learn more about this trial
A Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma
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