Oral Hedgehog Inhibitors in the Treatment of Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study

Study Overview
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Brief Summary
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Background: Oral hedgehog inhibitors vismodegib and sonidegib have been used for the treatment of locally advanced (laBCC), metastatic basal cell carcinoma (mBCC) and in basal cell nevus syndrome (BCNS) patients. In the Netherlands, targeted therapy with vismodegib and sonidegib has been available since 2013 and 2021, respectively. No direct comparative studies have been performed between the two oral hedgehog inhibitors (HHI) vismodegib and sonidegib yet . In addition, data for sonidegib are not yet available. Objective: The aim of this study is 1) to evaluate the effectiveness of oral HHIs in the treatment of laBCC, mBCC and BCNS patients and 2) to compare the oral HHIs vismodegib and sonidegib. Study design: prospective registration study that includes all patients, regardless of age and gender, with histologically proven basal cell carcinoma receiving treatment with either vismodegib or sonidegib in the Netherlands. Patient, tumor and treatment information was gathered from patient records. Main study parameters/endpoints: The primary outcome for measuring efficacy/tumor response was median progression free survival (PFS) where the decrease, stagnation or increase in tumor size is measured by maximum diameter. Secondary outcomes are frequency, severity and reversibility of treatment-emergent adverse events and disease-specific quality of life expressed as mean scores on the EORTC-QLQ-C30 and aBCCdex questionnaires.

Detailed Description
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This is a prospective registration study conducted in eight academic hospitals in the Netherlands. Vismodegib and sonidegib are currently only prescribed in academic hospitals in the Netherlands. Therefore, this multicenter approach with all academic centers in the Netherlands provides a complete insight into the prescription of these oral HHIs in the Netherlands. The study takes place at the dermatology and oncology department of Maastricht University Medical Center+ (MUMC+), Erasmus University Medical Center (Erasmus MC) Rotterdam, Netherlands Cancer Institute (NKI) Amsterdam, University Medical Center Groningen (UMCG), University Medical Center Utrecht (UMC Utrecht), Amsterdam University Medical Center (Amsterdam UMC), Radboud University Medical Center (Radboudumc) and Leiden University Medical Center (LUMC). All patients receiving at least one dose of vismodegib or sonidegib for the treatment of basal cell carcinoma (laBCC, mBCC, multiple BCCs in BCNS and in non-BCNS) (in regular care) will be included, provided they give permission and sign the informed consent form. Treating physicians then systematically register data on treatment using a uniform registration format. This registration includes the effectiveness of the drug measured by tumor diameter*, adverse events according to the CTCAE version 5.0, and data such as age, gender, World health organization (WHO) status, scores on the G8 questionnaire, medication use, comorbidities, indication, dosage, treatment duration, laboratory values, and reason for discontinuation of treatment. In addition, twice a year scores on the EORTC-QLQ-C30 and aBCCdex questionnaires are registered. All data will be extracted from electronic patient files en will be entered anonymously in a Castor database. The primary outcome for measuring efficacy/tumor response is median progression free survival (PFS) where the decrease, stagnation or increase in tumor size is measured by maximum tumor diameter*. Secondary outcomes are frequency, severity and reversibility of treatment-emergent adverse events and disease-specific quality of life expressed as mean scores on the EORTC-QLQ-C30 and aBCCdex questionnaires. In addition, the association of patient characteristics on drug efficacy and adverse events will be analysed. *In case of gorlin goltz syndrome or multiple BCCs, at least 3 target lesions are registered whose diameters are monitored over time.

Official Title
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Registration of Oral Hedgehog Inhibitors Vismodegib and Sonidegib in the Treatment of Advanced and Multiple Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study.

Conditions
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Basal Cell Carcinoma, Locally Advanced Basal Cell Carcinoma, Metastatic Basal Cell Carcinoma, Gorlin Syndrome, Basal Cell Nevus Syndrome, Carcinoma, Basal Cell, Carcinoma, Basal Cell Tumor, Skin Cancer, Neoplasm of Skin, Neoplasms, Basal Cell

Intervention / Treatment
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* Drug: Vismodegib
* Drug: Sonidegib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women All ages Diagnosed with locally advanced basal cell carcinoma (laBCC), metastatic basal cell carcinoma (mBCC), multiple basal cell carcinomas or Gorlin syndrome Use of oral hedgehog inhibitor vismodegib or sonidegib Exclusion Criteria: None
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oral hedgehog inhibitor<br>Oral hedgehog inhibitors vismodegib (Erivedge) or sonidegib (Odomzo) | Drug: Vismodegib<br>* Oral vismodegib (Erivedge), taken daily or every other day (depending on doctor's description)<br>* Other names: Erivedge;Drug: Sonidegib<br>* Sonidegib (Odomzo), taken daily or every other day (depending on doctor's description)<br>* Other names: Odomzo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median progression free survival | The main study outcome measure is the median progression free survival (PFS) where the decrease, stagnation or increase in tumor size is measured by maximum diameter. | though study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Frequency, severity and reversibility of treatment-emergent adverse events, measured according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | At baseline (start of treatment), after 1 month and every 3 months thereafter during use of vismodegib or sonidegib, at discontinuation of the treatment and 3 months after discontinuation of the treatment. | 
| Disease-specific quality of life | Disease-specific quality of life expressed as mean scores on the validated European Organisation for Research and Treatment of Cancer (EORTC) core quality of life (EORTC-QLQ-C30) questionnaire. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. | At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used. | 
| Disease-specific quality of life | Disease-specific quality of life expressed as mean scores on the validated advanced basal cell carcinoma index (aBCCdex) questionnaire. The aBCCdex consists of 26 questions related to symptoms, emotions, worry, avoidance behavior and influence on daily life. Scales range in score from 1 to 7 and from 1 to 6. A higher score correlates with a poorer quality of life. | At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral hedgehog inhibitors, Vismodegib, Sonidegib, Erivedge, Odomzo