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

Basal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00833417
• Other study ID #: SHH4476g
• Secondary ID: GO01541
• Status: Completed
• Phase: Phase 2
• First received: January 30, 2009
• Last updated: May 1, 2015
• Start date: February 2009
• Est. completion date: April 2014

Study information

• Verified date: May 2015
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: April 2014
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Basal Cell Carcinoma
• Carcinoma
• Carcinoma, Basal Cell

Intervention

Drug:
• Vismodegib 150 mg
Vismodegib 150 mg was provided in hard gelatin capsules.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	No
Secondary	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 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	No
Secondary	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 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	No
Secondary	Overall Survival	Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.	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	No
Secondary	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 90 weeks	No
Secondary	Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC	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.	From baseline through end of the study, up to 90 weeks	No