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

May 15, 2023 updated by: Maastricht University Medical Center

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Emmy Cruts, MD
  • Phone Number: +31(0)43 3877295
  • Email: e.cruts@mumc.nl

Study Locations

  • Netherlands
      • Groningen, Netherlands
        • Not yet recruiting
        • UMCG
        • Contact:
          • A.K.L. Reyners, MD, PhD
      • Utrecht, Netherlands
        • Recruiting
        • UMC Utrecht
        • Contact:
          • L.A. Devriese, MD, PhD
    • Gelderland
      • Nijmegen, Gelderland, Netherlands
        • Recruiting
        • Radboudumc
        • Contact:
          • S Lubeek, MD, PhD
    • Limburg
      • Maastricht, Limburg, Netherlands
        • Recruiting
        • Maastricht University Medical Center +
        • Principal Investigator:
          • Klara Mosterd, MD, PhD
        • Contact:
          • Emmy Cruts, MD
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands
        • Recruiting
        • Amsterdam UMC
        • Contact:
          • M.W. Bekkenk, MD, PhD
      • Amsterdam, Noord-Holland, Netherlands
        • Recruiting
        • Netherlands Cancer Institute - AVL
        • Contact:
          • B. Zupan, MD
    • Zuid-Holland
      • Leiden, Zuid-Holland, Netherlands
        • Recruiting
        • LUMC
        • Contact:
          • R. van Doorn, MD, PhD
      • Rotterdam, Zuid-Holland, Netherlands
        • Recruiting
        • Erasmus MC
        • Contact:
          • M. Wakkee, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Oral hedgehog inhibitor
Oral hedgehog inhibitors vismodegib (Erivedge) or sonidegib (Odomzo)
Drug: Vismodegib
Oral vismodegib (Erivedge), taken daily or every other day (depending on doctor's description)
Other Names:
  • Erivedge
Drug: Sonidegib
Sonidegib (Odomzo), taken daily or every other day (depending on doctor's description)
Other Names:
  • Odomzo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median progression free survival
Time Frame: 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.
though study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 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.
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
Time Frame: 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 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
Time Frame: 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.
At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Collaborators

Sun Pharmaceutical Industries Limited

Investigators

  • Principal Investigator: K Mosterd, MD, PhD, Maastricht University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2021

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

May 31, 2022

First Submitted That Met QC Criteria

July 14, 2022

First Posted (Actual)

July 19, 2022

Study Record Updates

Last Update Posted (Actual)

May 16, 2023

Last Update Submitted That Met QC Criteria

May 15, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METC 2018-0452-A-10 Vismodegib

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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