Clinical trial NCT00833417: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Basal Cell Carcinoma
Keywords: BCC
Hedgehog Pathway Inhibitor
Hedgehog
Basal Cell Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-02-02
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective Response (OR) Determined by the Independent Review Facility
timeFrame: 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 outcomes:
measure: Duration of Objective Response (OR) Determined by the Independent Review Facility
timeFrame: 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
measure: Progression-free Survival (PFS) Determined by the Independent Review Facility
timeFrame: 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
measure: Overall Survival
timeFrame: 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
measure: Change From Baseline in Short Form 36 (SF-36) Health Survey Scores
timeFrame: Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks
measure: Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC
timeFrame: From baseline through end of the study, up to 90 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Stanford
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Ormond Beach
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Sioux City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Lebanon
country: United States
state: New Hampshire
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Kogarah, New South Wales
country: Australia
city: Melbourne
country: Australia
city: Woolloongabba
country: Australia
city: Bruxelles
country: Belgium
city: Wilrijk
country: Belgium
city: Lille
country: France
city: Nantes Cedex 1
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Essen
country: Germany
city: Kiel
country: Germany
city: Tübingen
country: Germany
city: Wurzburg
country: Germany
city: London
country: United Kingdom
city: Poole
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Jeannie Hou, M.D.
role: STUDY_DIRECTOR
References:
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.
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.
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.