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

Recruiting

• Conditions: Basal Cell Carcinoma; Locally Advanced Basal Cell Carcinoma; Basal Cell Nevus Syndrome; Metastatic Basal Cell Carcinoma; Gorlin Syndrome; Carcinoma, Basal Cell; Carcinoma; Basal Cell Tumor; Skin Cancer; Neoplasm of Skin
• Interventions: Drug: Vismodegib; Drug: Sonidegib

• Registration Number: NCT05463757
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-11-01
• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-07-14
• Study First Posted: 2022-07-19
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-04
• Primary Completion: 2026-06
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Oral hedgehog inhibitor	Sonidegib	Oral hedgehog inhibitors vismodegib (Erivedge) or sonidegib (Odomzo)
Oral hedgehog inhibitor	Vismodegib	Oral hedgehog inhibitors vismodegib (Erivedge) or sonidegib (Odomzo)

Primary Outcome Measures

Name	Time	Method
Median progression free survival	though study completion, an average of 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Adverse events	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.	Frequency, severity and reversibility of treatment-emergent adverse events, measured according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Disease-specific quality of life	At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used.	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.

Trial Locations

Locations (8)

Radboudumc; 🇳🇱 Nijmegen, Gelderland, Netherlands

Maastricht University Medical Center +; 🇳🇱 Maastricht, Limburg, Netherlands

Amsterdam UMC; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Netherlands Cancer Institute - AVL; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

LUMC; 🇳🇱 Leiden, Zuid-Holland, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

UMCG; 🇳🇱 Groningen, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, Netherlands