A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma

A Pivotal Phase II, Multicenter, Single-arm, Two-cohort Trial Evaluating the Efficacy and Safety of GDC-0449 in Patients With Advanced Basal Cell Carcinoma

This is a Phase II, single-arm, two-cohort multicenter clinical trial evaluating the efficacy and safety of vismodegib (GDC-0449) in patients with advanced basal cell carcinoma. All patients receive vismodegib until evidence of progression, intolerable toxicities most probably attributable to vismodegib, or withdrawal from the study.

Study Overview

• Status: Completed
• Conditions: Basal Cell Carcinoma
• Intervention / Treatment: Drug: Vismodegib 150 mg

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess AleXandra Hospital; Department of Medical Oncology
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk, Apotheek
• France
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme; Clinique Dermatologique
  • Paris, France, 75475
    • Hopital Saint Louis; Dermatologie 1
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud; Dermatologie
• Germany
  • Essen, Germany, 45122
    • Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig
  • Tübingen, Germany, 72076
    • Universitaets-Hautklinik Tuebingen
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg; Derma
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital - London
  • Poole, United Kingdom, BH15 2JB
    • Poole Hospital; Dorset Cancer Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90025
      • Angeles Clinic & Rsch Inst
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • San Francisco, California, United States, 94115
      • Univ of Calif-San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Hlth Sci Ctr
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Advanced Derm & Cosmetic Surg
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology/Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Univ Med Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester; Medical Oncology
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • VA Southern Nevada Healthcare
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Med Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine; Dermatology
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305v
      • Univ No Carolina School of Med; Physicians Office Bldg
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hosp
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Inst
  • Texas
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women ≥ 18 years of age.
• For patients with metastatic basal cell carcinoma (BCC), histological confirmation of distant BCC metastasis (eg, lung, liver, lymph nodes, or bone), with metastatic disease that is Response Evaluation Criteria in Solid Tumors (RECIST) measurable using computed tomography (CT) or magnetic resonance imaging (MRI).
• For patients with locally advanced BCC, histologically confirmed disease that is considered to be inoperable.
• For patients with locally advanced BCC, radiotherapy must have been previously administered for their locally advanced BCC, unless radiotherapy is contraindicated or inappropriate. For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation.
• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 12 months after discontinuation of vismodegib (GDC-0449).
• For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 3 months after discontinuation of vismodegib.

Exclusion Criteria:

• Prior treatment with vismodegib or other Hedgehog pathway inhibitors.
• Pregnancy or lactation.
• Life expectancy of < 12 weeks.
• Patients with superficial multifocal BCC who may be considered unresectable due to breadth of involvement.
• Concurrent non-protocol-specified anti-tumor therapy (eg, chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy).
• Recent, current, or planned participation in an experimental drug study.
• History of other malignancies within 3 years of the first day of treatment with vismodegib in this study (Day 1), except for tumors with a negligible risk for metastasis or death, such as adequately treated squamous-cell carcinoma of the skin, ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix.
• Uncontrolled medical illnesses such as infection requiring treatment with intravenous antibiotics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vismodegib 150 mg; Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.	Drug: Vismodegib 150 mg; Vismodegib 150 mg was provided in hard gelatin capsules.; Other Names: GDC-0449

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR) Determined by the Independent Review Facility	OR=complete (CR) or partial response (PR). Metastatic-CR:Disappearance of all targets. PR:≥30% decreased sum of longest diameter (SLD) of targets compared to baseline (B). Locally advanced-Response=No progressive disease (PD) and ≥30% decreased SLD from baseline (radiography [R]) or ≥30% decreased SLD from B (externally visible dimension [EVD]) or completely resolved ulceration. CR:Response with no residual BCC on tumor biopsy (otherwise response was PR). PD:Any of ≥20% increased SLD from nadir (R or EVD), new ulceration, new lesions (R or physical exam) or non-target lesion progression by R.	At Baseline and once every 8 weeks thereafter (responses confirmed within ≥4 weeks) until the end of study (up to the clinical cutoff date of 26 November 2010, up to 90 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Objective Response (OR) Determined by the Independent Review Facility	Duration of OR was defined as the time from the initial CR or PR to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.	From initial OR until the earliest documented disease progression (PD) or death (until clinical cutoff date of 26 November 2010, up to 90 weeks)
Progression-Free Survival (PFS) Determined by the Independent Review Facility	PFS was defined as the time from start of treatment to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.	From the initial dose of study drug until the earliest documented disease progression (PD) or death (up to the clinical cutoff date of 28 November 2011, up to 2 years, 5.5 months)
Overall Survival	Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.	From the initial dose of study drug until death from any cause (up to the clinical cutoff date of 30 May 2013, up to 4 years)
Change From Baseline in Short Form 36 (SF-36) Health Survey Scores	The SF-36 Health Survey (Version 2) uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.	Baseline, Week 12, Week 24, and at the end of the study or early termination visit (up to the clinical cutoff date of 26 November 2010, up to 90 weeks)
Percentage of Participants With Absence of Residual Basal Cell Carcinoma (BCC) in the Efficacy-Evaluable Locally Advanced BCC Cohort	In patients with locally advanced BCC, the histopathological effect of vismodegib was determined in tissue biopsies obtained at baseline (prior to study drug dosing) and at 24 weeks after the start of vismodegib treatment, if the patient was still on study without evidence of progression, or at the investigator's assessment of best clinical response (or best clinical/RECIST response), if occurring prior to 24 weeks. At any time during a patient's participation in the study, an optional tumor biopsy might have been requested to clarify the response status of the patient. Reported is the percentage of efficacy-evaluable patients with locally advanced BCC pathology that was confirmed in a baseline biopsy who had an absence of residual BCC post-baseline as assessed by an independent pathological review.	At Baseline and 24 weeks, and at any optional point post-baseline through end of the study (up to the clinical cutoff date of 26 November 2010, up to 90 weeks)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Jeannie Hou, M.D., Genentech, Inc.

Publications and helpful links

General Publications

• Chang AL, Arron ST, Migden MR, Solomon JA, Yoo S, Day BM, McKenna EF, Sekulic A. Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials. Orphanet J Rare Dis. 2016 Sep 1;11(1):120. doi: 10.1186/s13023-016-0506-z.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2009
• Primary Completion (Actual): November 26, 2010
• Study Completion (Actual): April 9, 2014

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimated): February 2, 2009

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hedgehog Pathway Inhibitor; BCC; Hedgehog; Basal Cell Cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Basal Cell; Carcinoma, Basal Cell; HhAntag691
• Other Study ID Numbers: SHH4476g; GO01541

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing