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

NCT05463757 | Recruiting

• 1 other identifier: METC 2018-0452-A-10 Vismodegib
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 8

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

• 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

  At the start of treatment and every 6 months thereafter, until vismodegib or sonidegib is no longer used.

Study Arms (1)

Oral hedgehog inhibitor

Oral hedgehog inhibitors vismodegib (Erivedge) or sonidegib (Odomzo)

Drug: Vismodegib; Drug: Sonidegib

Interventions

Vismodegib DRUG

Oral vismodegib (Erivedge), taken daily or every other day (depending on doctor's description)

Also known as: Erivedge

Oral hedgehog inhibitor

Sonidegib DRUG

Sonidegib (Odomzo), taken daily or every other day (depending on doctor's description)

Also known as: Odomzo

Oral hedgehog inhibitor

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• None

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Sun Pharmaceutical Industries Limited: collaborator

Study Sites (8)

Radboudumc

Nijmegen, Gelderland, Netherlands

RECRUITING

Maastricht University Medical Center +

Maastricht, Limburg, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, North Holland, Netherlands

RECRUITING

Netherlands Cancer Institute - AVL

Amsterdam, North Holland, Netherlands

RECRUITING

UMCG

Groningen, Provincie Groningen, Netherlands

NOT YET RECRUITING

LUMC

Leiden, South Holland, Netherlands

RECRUITING

Erasmus MC

Rotterdam, South Holland, Netherlands

RECRUITING

UMC Utrecht

Utrecht, Utrecht, Netherlands

RECRUITING

Related Publications (13)

• Verkouteren BJA, Wakkee M, Reyners AKL, Nelemans P, Aarts MJB, Racz E, Terra JB, Devriese LA, Alers RJ, Kapiteijn E, van Doorn R, Bekkenk MW, Reinders MGHC, Mosterd K. Eight years of experience with vismodegib for advanced and multiple basal cell carcinoma patients in the Netherlands: a retrospective cohort study. Br J Cancer. 2021 Mar;124(7):1199-1206. doi: 10.1038/s41416-020-01220-w. Epub 2021 Jan 19.

  PMID: 33462360 BACKGROUND

• Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9. doi: 10.1056/NEJMoa1113713.

  PMID: 22670903 BACKGROUND

• Basset-Seguin N, Hauschild A, Kunstfeld R, Grob J, Dreno B, Mortier L, Ascierto PA, Licitra L, Dutriaux C, Thomas L, Meyer N, Guillot B, Dummer R, Arenberger P, Fife K, Raimundo A, Dika E, Dimier N, Fittipaldo A, Xynos I, Hansson J. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. Eur J Cancer. 2017 Nov;86:334-348. doi: 10.1016/j.ejca.2017.08.022. Epub 2017 Nov 5.

  PMID: 29073584 BACKGROUND

• Dreno B, Kunstfeld R, Hauschild A, Fosko S, Zloty D, Labeille B, Grob JJ, Puig S, Gilberg F, Bergstrom D, Page DR, Rogers G, Schadendorf D. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):404-412. doi: 10.1016/S1470-2045(17)30072-4. Epub 2017 Feb 8.

  PMID: 28188086 BACKGROUND

• Ben Ishai M, Tiosano A, Fenig E, Ben Simon G, Yassur I. Outcomes of Vismodegib for Periocular Locally Advanced Basal Cell Carcinoma From an Open-label Trial. JAMA Ophthalmol. 2020 Jul 1;138(7):749-755. doi: 10.1001/jamaophthalmol.2020.1539.

  PMID: 32407451 BACKGROUND

• Dutch Society for Dermatology and Venereology (NVDV). Basal Cell Carcinoma: Dutch Guideline (Dutch Society for Dermatology and Venereology (NVDV). 2015).

  BACKGROUND

• Xie P, Lefrancois P. Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: A systematic review and meta-analysis. J Am Acad Dermatol. 2018 Dec;79(6):1089-1100.e17. doi: 10.1016/j.jaad.2018.07.004. Epub 2018 Jul 10.

  PMID: 30003981 BACKGROUND

• Sekulic A, Migden MR, Basset-Seguin N, Garbe C, Gesierich A, Lao CD, Miller C, Mortier L, Murrell DF, Hamid O, Quevedo JF, Hou J, McKenna E, Dimier N, Williams S, Schadendorf D, Hauschild A; ERIVANCE BCC Investigators. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017 May 16;17(1):332. doi: 10.1186/s12885-017-3286-5.

  PMID: 28511673 BACKGROUND

• Sekulic A, Migden MR, Lewis K, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Dirix L, Hou J, Yue H, Hauschild A; ERIVANCE BCC investigators. Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC. J Am Acad Dermatol. 2015 Jun;72(6):1021-6.e8. doi: 10.1016/j.jaad.2015.03.021.

  PMID: 25981002 BACKGROUND

• Dummer R, Ascierto PA, Basset-Seguin N, Dreno B, Garbe C, Gutzmer R, Hauschild A, Krattinger R, Lear JT, Malvehy J, Schadendorf D, Grob JJ. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. J Eur Acad Dermatol Venereol. 2020 Sep;34(9):1944-1956. doi: 10.1111/jdv.16230. Epub 2020 Mar 4.

  PMID: 31990414 BACKGROUND

• Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer. 2008 Oct;8(10):743-54. doi: 10.1038/nrc2503.

  PMID: 18813320 BACKGROUND

• Lewis K, Dummer R, Farberg AS, Guminski A, Squittieri N, Migden M. Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial. Dermatol Ther (Heidelb). 2021 Dec;11(6):2225-2234. doi: 10.1007/s13555-021-00619-4. Epub 2021 Oct 20.

  PMID: 34669179 BACKGROUND

• Villani A, Costa C, Fabbrocini G, Ruggiero A, Scalvenzi M. Dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor sonidegib to manage adverse effects: A retrospective case series. J Am Acad Dermatol. 2021 Apr;84(4):e211-e212. doi: 10.1016/j.jaad.2020.12.006. Epub 2020 Dec 7. No abstract available.

  PMID: 33301802 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Basal Cell; Basal Cell Nevus Syndrome; Carcinoma; Neoplasms, Basal Cell; Skin Neoplasms

Interventions

HhAntag691; sonidegib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• K Mosterd, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmy Cruts, MD

CONTACT

+31(0)43 3877295; e.cruts@mumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: July 19, 2022
• Study Start: November 1, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03

Locations

NL (8)