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

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ClinicalTrials.gov Identifier: NCT03534947
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
Melanoma Institute Australia

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.

Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma Basal Cell Carcinoma of Skin, Site Unspecified Skin Cancer Invasive Carcinoma Drug: Sonidegib Drug: Imiquimod Procedure: Surgery Other: Best supportive care Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 23, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Excision of remnant invasive basal cell carcinoma

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




Primary Outcome Measures :
  1. Neoadjuvant treatment response determined by optical coherence tomography [ Time Frame: 12 weeks ]
    The size and spread of abnormal skin structures associated with basal cell carcinoma detected by optical coherence tomography.


Secondary Outcome Measures :
  1. Neoadjuvant treatment response determined by histopathology [ Time Frame: 12 weeks ]
    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.

  2. Histologic response to neoadjuvant treatment in basal cell carcinoma sub types [ Time Frame: 12 weeks ]
    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.

  3. Response to neoadjuvant treatment in basal cell carcinoma sub types measured with optical coherence tomography. [ Time Frame: 12 weeks ]
    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.

  4. Recurrence rate [ Time Frame: 6 and 12 months after surgery or at the end of 6 weeks of treatment with imiquimiod. ]
    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.

  5. Drug related adverse reactions [ Time Frame: 12 weeks ]
    The proportion of patients experiencing any adverse drug reactions graded according to CTCAE version 4.

  6. Discontinuation of sonidegib due to adverse reactions [ Time Frame: 12 weeks ]
    The proportion of patients who discontinue sonideigb because of adverse drug reactions.

  7. Quality of life based on SKINDEX-16 [ Time Frame: Weeks 12 and 18 and months 6 and 12. ]
    The scores obtained from the validated SKINDEX-16 quality of life questionnaire compared to baseline.

  8. Patient rated cosmetic outcome after neoadjuvant treatment followed by surgery [ Time Frame: Week 12 ]
    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.

  9. Surgeon rated cosmetic outcome after neoadjuvant treatment followed by surgery [ Time Frame: Week 12 ]
    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.

  10. Patient rated cosmetic outcome after neoadjuvant treatment [ Time Frame: Week 12 ]
    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.

  11. Surgeon rated cosmetic outcome after neoadjuvant treatment [ Time Frame: Week 12 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03534947


Contacts
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Contact: Pascale Guitera, MD PhD +61299117296 pascale.guitera@melanoma.org.au

Locations
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Australia, New South Wales
Melanoma Institute Australia Recruiting
North Sydney, New South Wales, Australia, 2060
Contact: Pascal Guitera, MD PhD    +61299117296    pascale.guitera@melanoma.org.au   
Principal Investigator: Pascale Guitera         
Sponsors and Collaborators
Melanoma Institute Australia
Investigators
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Study Director: Pascale Guitera, MD PhD Melanoma Institute Australia

Publications:
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Responsible Party: Melanoma Institute Australia
ClinicalTrials.gov Identifier: NCT03534947     History of Changes
Other Study ID Numbers: MIA2017/CT/220
HREC file number 18/087 ( Other Identifier: Human Research Ethics Committee )
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Melanoma Institute Australia:
Neoadjuvant
Sonidegib
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Basal Cell
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell
Neoplasms by Site
Skin Diseases
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers