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

• ClinicalTrials.gov Identifier: NCT00833417
• Recruitment Status: Completed
• First Posted: February 2, 2009
• Results First Posted: April 30, 2012
• Last Update Posted: May 20, 2015
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Study Description

Brief Summary:

This was 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 received vismodegib until evidence of progression, intolerable toxicities most probably attributable to vismodegib, or withdrawal from the study.

Condition or disease	Intervention/treatment	Phase
Basal Cell Carcinoma	Drug: Vismodegib 150 mg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: February 2009
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: April 2014

Arms and Interventions

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 Name: GDC-0449

Outcome Measures

Primary Outcome Measures :

1. Objective Response (OR) Determined by the Independent Review Facility [ Time Frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks ]
   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.

Secondary Outcome Measures :

1. Duration of Objective Response (OR) Determined by the Independent Review Facility [ Time Frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks ]
   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.
2. Progression-free Survival (PFS) Determined by the Independent Review Facility [ Time Frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks ]
   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.
3. Overall Survival [ Time Frame: From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks ]
   Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.
4. Change From Baseline in Short Form 36 (SF-36) Health Survey Scores [ Time Frame: Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks ]
   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.
5. Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC [ Time Frame: From baseline through end of the study, up to 90 weeks ]
   In patients with locally advanced BCC, the histopathological effect of vismodegib was determined in tissue biopsies obtained at baseline and following vismodegib treatment. Reported are the percentage of patients with pathology confirmed BCC in baseline biopsy who had an absence of residual BCC post-baseline as assessed by an independent pathological review.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Scottsdale, Arizona, United States, 85259

United States, California

Los Angeles, California, United States, 90025

San Francisco, California, United States, 94115

Stanford, California, United States, 94305

United States, Colorado

Aurora, Colorado, United States, 80045

United States, Florida

Ormond Beach, Florida, United States, 32174

United States, Illinois

Chicago, Illinois, United States, 60611

United States, Iowa

Sioux City, Iowa, United States, 51101

United States, Maryland

Baltimore, Maryland, United States, 21231-1000

United States, Massachusetts

Boston, Massachusetts, United States, 02114

Boston, Massachusetts, United States, 02215

United States, Minnesota

Rochester, Minnesota, United States, 55905

United States, Nevada

Las Vegas, Nevada, United States, 89103

United States, New Hampshire

Lebanon, New Hampshire, United States, 03756

United States, New York

New York, New York, United States, 10029

United States, North Carolina

Chapel Hill, North Carolina, United States, 27599-7305

United States, Ohio

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Nashville, Tennessee, United States, 37203

United States, Texas

Houston, Texas, United States, 77030-4095

Australia

Kogarah, New South Wales, Australia, 2217

Melbourne, Australia, 3002

Woolloongabba, Australia, 4102

Belgium

Bruxelles, Belgium, 1000

Wilrijk, Belgium, 2610

France

Lille, France, 59037

Nantes Cedex 1, France, 44093

Paris, France, 75010

Pierre Benite, France, 69495

Germany

Essen, Germany, 45122

Kiel, Germany, 24105

Tübingen, Germany, 72076

Wurzburg, Germany, 97080

United Kingdom

London, United Kingdom, SW3 6JJ

Poole, United Kingdom, BH15 2JB

Sponsors and Collaborators

Genentech, Inc.

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum in: BMC Cancer. 2019 Apr 18;19(1):366.

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.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00833417
• Other Study ID Numbers: SHH4476g; GO01541
• First Posted: February 2, 2009
• Results First Posted: April 30, 2012
• Last Update Posted: May 20, 2015
• Last Verified: May 2015

Keywords provided by Genentech, Inc.:

BCC; Hedgehog Pathway Inhibitor; Hedgehog; Basal Cell Cancer

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Basal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell