Clinical trial NCT05463757: Oral Hedgehog Inhibitors in the Treatment of Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study
Official title: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Keywords: Oral hedgehog inhibitors
Vismodegib
Sonidegib
Erivedge
Odomzo
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Sun Pharmaceutical Industries Limited
First posted: 2022-07-19
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All men and women, regardless of age, diagnosed with advanced basal cell carcinoma, metastatic basal cell carcinoma, multiple basal cell carcinomas or Gorlin syndrome, for which an oral hedgehog inhibitor (vismodegib or sonidegib) is used in the Netherlands.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median progression free survival
timeFrame: though study completion, an average of 3 years
Secondary outcomes:
measure: Adverse events
timeFrame: 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.
measure: Disease-specific quality of life
timeFrame: At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used.
measure: Disease-specific quality of life
timeFrame: At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used.
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center +
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - AVL
state: Noord-Holland
city: Leiden
country: Netherlands
facility: LUMC
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: UMCG
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Maastricht University Medical Center
name: K Mosterd, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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