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

Purpose

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 will receive vismodegib until evidence of progression, intolerable toxicities most probably attributable to vismodegib, or withdrawal from the study.

Condition	Intervention	Phase
Basal Cell Carcinoma	Drug: Vismodegib 150 mg	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Multicenter, Single-Arm, Two-Cohort Trial Evaluating the Efficacy and Safety of Vismodegib (GDC-0449) in Patients With Advanced Basal Cell Carcinoma

Resource links provided by NLM:

Drug Information available for: Vismodegib

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.
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 ] [ Designated as safety issue: No ]
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.
Number 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 ] [ Designated as safety issue: No ]
In patients with locally advanced BCC, the histopathological effect of vismodegib was determined in tissue biopsies obtained at baseline and following vismodegib treatment. A histopathological response was defined as the absence of residual BCC post-baseline assessed by the independent pathological review.

Enrollment:	104
Study Start Date:	February 2009
Estimated Study Completion Date:	February 2014
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00833417

Show 35 Study Locations

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Jeannie Hou, M.D.

Genentech

More Information

No publications provided by Genentech

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

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.

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00833417 History of Changes
Other Study ID Numbers:	SHH4476g, GO01541
Study First Received:	January 30, 2009
Results First Received:	February 23, 2012
Last Updated:	March 1, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

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

ClinicalTrials.gov processed this record on May 23, 2013