A Study of Two Vismodegib Regimens in Participants With Multiple Basal Cell Carcinomas

A Randomized, Double-blinded, Regimen-controlled, Phase II, Multicenter Study to Assess the Efficacy and Safety of Two Different Vismodegib Regimens in Patients With Multiple Basal Cell Carcinomas

This randomized, double-blind, regimen-controlled, phase II, multicenter study will assess the efficacy and safety of two different vismodegib regimens in participants with multiple basal cell carcinoma. Participants will receive vismodegib 150 mg orally once daily either in an intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo (Arm A) or as 24 weeks induction followed by an intermittent schedule of 8 weeks placebo followed by 8 weeks vismodegib (Arm B). Anticipated time on study treatment is 72 weeks.

Study Overview

• Status: Completed
• Conditions: Basal Cell Carcinoma
• Intervention / Treatment: Drug: Vismodegib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • LKH Innsbruck; Universitätsklinik für Dermatologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Dermatologie
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • UBC Department of Dermatology & Skin Sciences
  • Ontario
    • Burlington, Ontario, Canada, L7N 3N2
      • Dermetics
  • Quebec
    • Montreal, Quebec, Canada, L2K 4L5
      • Innovaderm Research Inc.
• France
  • Amiens, France, 80054
    • Chu Amiens - Hopital Sud
  • Bordeaux, France, 33075
    • Hopital Saint Andre CHU De Bordeaux; Dermatologie
  • Dijon, France, 21079
    • Chu Site Du Bocage;Dermatologie
  • Limoges, France, 87042
    • Hopital Dupuytren; Dermatologie
  • Marseille, France, 13385
    • Hopital Timone Adultes; Dermatologie
  • Montpellier, France, 34295
    • Hopital Saint Eloi; CHU de Montpellier; Svc de Dermatologie
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme; Clinique Dermatologique
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pau, France, 64046
    • Ch Francois Mitterrand; Medecine Oncologie
  • Saint-Etienne, France, 42277
    • Hopital Nord ; Dermatologie
• Germany
  • Essen, Germany, 45122
    • Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
  • Frankfurt, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
  • Gera, Germany, 07548
    • SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
  • Kiel, Germany, 24105
    • UNI-Klinikum Campus Kiel Klinik f.Dermatologie Tagesklinik f.Dermatologie
  • München, Germany, 80337
    • Klinikum der LMU München; Klinik und Poliklinik für Dermatologie und Allergologie
  • Münster, Germany, 48157
    • Fachklinik Hornheide; Dermatologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen Universitäts-Hautklinik
• Italy
  • Abruzzo
    • L'Aquila, Abruzzo, Italy, 67100
      • Ospedale San Salvatore (ASL-01); Dip. di Dermatologia U.O.S. di Dermatologia Oncol
  • Emilia-Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Arcispedale Santa Maria Nuova; Dermatologia
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Università di Brescia; Dipartimento di Dermatologia
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Azienda Ospedaliera Citta della Salute e della Scienza di Torino
  • Toscana
    • Firenze, Toscana, Italy, 50125
      • Ospedale IOT- Palagi Dermatologia 2
• Mexico
  • Mexico, Mexico, 14080
    • Hospital General Dr. Manuel Gea Gonzalez; Dermatology
  • Mexico City, Mexico, 06726
    • Hospital General de México
• Netherlands
  • Amsterdam, Netherlands, 1007 MB
    • VU MEDISCH CENTRUM;Afdeling Dermatologie
  • Groningen, Netherlands, 9713 GZ
    • Academ Ziekenhuis Groningen; Medical Oncology
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Centre; Dermatologie
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center; General Oncology Department
  • Moscow, Russian Federation, 115478
    • FSBI "Russian Oncology Research Center n.a. N. N. Blokhin" of Ministry of Health of the Russian Fed
  • Saint-Petersburg, Russian Federation, 197022
    • City Clinical Oncology Dispensary
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Farmacia
  • Guadalajara, Spain, 19002
    • Hospital General Universitario de Guadalajara; Servicio de Dermatologia
  • Valencia, Spain, 46009
    • Instituto Valenciano Oncologia; Oncologia Medica
  • Valencia, Spain, 41014
    • Hospital General Universitario de Valencia; Servicio de oncologia
  • Malaga
    • Málaga, Malaga, Spain, 29600
      • Hospital Costa Del Sol; Servicio de Dermatologia
• United States
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associate
    • Palo Alto, California, United States, 94305
      • Stanford University
    • San Diego, California, United States, 92117
      • Skin Surgery Med Group, Inc
    • Santa Rosa, California, United States, 95403
      • California Pacific Medical Center Research Institute
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Advanced Derm & Cosmetic Surg
    • Plantation, Florida, United States, 33324
      • Skin and Cancer Associates and the Center for Cosmetic Enhancement
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Clinic
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Laser & Skin Surgery Center of Indiana
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • Beverly Hospital;Oncology Center Pharmacy
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University School of Medicine; Department of Dermatology
  • New York
    • Smithtown, New York, United States, 11787
      • Long Island Skin Cancer and Dermatologic Surgery
    • West Islip, New York, United States, 11795
      • Mariwalla Dermatology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27106
      • The Skin Surgery Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Dermatology and Laser Center of Charleston PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants, >/= 18 years of age
• Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least 6 clinically evident basal cell carcinomas at the time of randomization, of which 3 measure 5 mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions
• Histopathologic confirmation that at least one of the three target lesions is basal cell carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Adequate renal and hepatic function and hematopoietic capacity
• Women of childbearing potential must agree to use contraception as defined by protocol during treatment and for at least 9 months after completion of study treatment
• Male participants with female partners of childbearing potential must agree to use contraception as defined by protocol during treatment and for 2 months after completion of study treatment

Exclusion Criteria:

• Inability or unwillingness to swallow capsules
• Pregnant or breastfeeding women
• Any metastatic basal cell carcinoma
• Locally advanced basal cell carcinoma lesion that is considered to be inoperable or to have medical contraindications to surgery
• Recent (i.e., within the past 28 days prior to randomization) or current participation in another experimental drug study
• Known or suspected alcohol abuse
• One of the following known rare hereditary conditions: galactose intolerance, primary hypolactasia or glucose-galactose malabsorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vismodegib Intermittent Schedule; Vismodegib intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo, repeated 3 times with a final course of vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up	Drug: Vismodegib; Vismodegib 150 mg hard gelatin capsule orally once daily; Other Names: Erivedge®; Drug: Placebo; Vismodegib placebo orally once daily
EXPERIMENTAL: Vismodegib Induction Followed by Intermittent Schedule; Vismodegib beginning with 24 weeks induction followed by intermittent schedule 8 weeks placebo, 8 weeks vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up	Drug: Vismodegib; Vismodegib 150 mg hard gelatin capsule orally once daily; Other Names: Erivedge®; Drug: Placebo; Vismodegib placebo orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment)	The total number of clinically evident basal cell carcinomas = the total number of target and/or non-target lesions present in individual participants.	Baseline; Week 73

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues	The percentage of participants who discontinued study treatment (due either to adverse event, refusal of treatment, or withdrawal of consent) was summarized by treatment group.	Baseline to Week 73
Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73	The three target basal cell carcinoma lesions = the three largest visible lesions, at least 5 mm in the longest diameter, in individual participants.	Baseline; Week 73
Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73		Baseline; Week 73
Percentage of Participants With New Basal Cell Carcinomas at Week 73		Baseline; Week 73
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate)		Baseline; Week 85
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate)		Baseline; Week 97
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate)		Baseline; Week 125
Percentage of Participants Experiencing Any Adverse Event		Up to 125 weeks
Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73	The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their symptoms, and their answers were combined into a composite Symptom Domain Score. Scores range from 0 ("never bothered") to 100 ("always bothered").	Baseline; Week 73
Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73	The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their emotional state, and their answers were combined into a composite Emotion Domain Score. Scores range from 0 ("never bothered") to 100 ("always bothered").	Baseline; Week 73
Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73	The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their ability to function, and answers were combined into a composite Function Domain Score. Scores range from 0 ("never bothered") to 100 ("always bothered").	Baseline; Week 73

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Jacobsen AA, Kydd AR, Strasswimmer J. Practical management of the adverse effects of Hedgehog pathway inhibitor therapy for basal cell carcinoma. J Am Acad Dermatol. 2017 Apr;76(4):767-768. doi: 10.1016/j.jaad.2016.04.063. No abstract available.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 30, 2013
• Primary Completion (ACTUAL): August 27, 2015
• Study Completion (ACTUAL): August 31, 2016

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 19, 2013
• First Posted (ESTIMATE): March 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2017
• Last Update Submitted That Met QC Criteria: August 30, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Cysts; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Stomatognathic Diseases; Bone Diseases; Neoplastic Syndromes, Hereditary; Jaw Diseases; Abnormalities, Multiple; Bone Diseases, Developmental; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Neoplasms, Basal Cell; Carcinoma; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell
• Other Study ID Numbers: MO28295; 2012-003305-10 (EUDRACT_NUMBER)