Back to resultsA Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma
Primary Purpose
Basal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vismodegib 150 mg
Sponsored by
About this trial
This is an interventional treatment trial for Basal Cell Carcinoma focused on measuring BCC, Hedgehog Pathway Inhibitor, Hedgehog, Basal Cell Cancer
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vismodegib 150 mg
Arm Description
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Overall Survival
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
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00833417
Brief Title
A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma
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 Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma
Keywords
BCC, Hedgehog Pathway Inhibitor, Hedgehog, Basal Cell Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
104 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vismodegib 150 mg
Arm Type
Experimental
Arm Description
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Intervention Type
Drug
Intervention Name(s)
Vismodegib 150 mg
Other Intervention Name(s)
GDC-0449
Intervention Description
Vismodegib 150 mg was provided in hard gelatin capsules.
Primary Outcome Measure Information:
Title
Objective Response (OR) Determined by the Independent Review Facility
Description
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.
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
Secondary Outcome Measure Information:
Title
Duration of Objective Response (OR) Determined by the Independent Review Facility
Description
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.
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
Title
Progression-free Survival (PFS) Determined by the Independent Review Facility
Description
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.
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
Title
Overall Survival
Description
Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.
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
Title
Change From Baseline in Short Form 36 (SF-36) Health Survey Scores
Description
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.
Time Frame
Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks
Title
Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC
Description
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.
Time Frame
From baseline through end of the study, up to 90 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeannie Hou, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-1000
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89103
Country
United States
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7305
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4095
Country
United States
City
Kogarah, New South Wales
ZIP/Postal Code
2217
Country
Australia
City
Melbourne
ZIP/Postal Code
3002
Country
Australia
City
Woolloongabba
ZIP/Postal Code
4102
Country
Australia
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
City
Lille
ZIP/Postal Code
59037
Country
France
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
City
Paris
ZIP/Postal Code
75010
Country
France
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
City
Essen
ZIP/Postal Code
45122
Country
Germany
City
Kiel
ZIP/Postal Code
24105
Country
Germany
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
City
Wurzburg
ZIP/Postal Code
97080
Country
Germany
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
City
Poole
ZIP/Postal Code
BH15 2JB
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28511673
Citation
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.
Results Reference
derived
PubMed Identifier
27581207
Citation
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.
Results Reference
derived
PubMed Identifier
22670903
Citation
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.
Results Reference
derived
Learn more about this trial
A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma
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