STEVIE: A Study of Vismodegib in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma

Study Overview
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Brief Summary
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This single-arm, open-label, multi-center study will evaluate the safety and efficacy of vismodegib (GDC-0449) in patients with locally advanced or metastatic basal cell carcinoma. Patients will receive oral doses of vismodegib 150 mg once daily until disease progression or unacceptable toxicity.

Official Title
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A Single Arm, Open-label, Phase II, Multicentre Study, to Assess the Safety of Vismodegib (GDC-0449) in Patient With Locally Advanced or Metastatic Basal Cell Carcinoma (BCC)

Conditions
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Basal Cell Carcinoma

Intervention / Treatment
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* Drug: vismodegib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/=18 years of age Metastatic or locally advanced basal cell carcinoma considered inoperable or that surgery is contraindicated and radiotherapy is contraindicated or inappropriate Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Exclusion Criteria: Concurrent anti-tumor therapy Completion of the most recent anti-tumor therapy less than 21 days prior to the initiation of treatment Uncontrolled medical illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vismodegib - Locally Advanced<br>Participants received vismodegib 150 mg orally once a day until one of the following occurs: Disease progression, intolerable toxicity most probably attributable to vismodegib, consent withdrawal, death, study termination by the Sponsor, or other reason deemed by the Investigator. vismodegib: 150 mg once daily until disease progression or unacceptable toxicity | Drug: vismodegib<br>* 150 mg once daily until disease progression or unacceptable toxicity<br>|
| Experimental: Vismodegib - Metastatic<br>Participants received vismodegib 150 mg orally once a day until one of the following occurs: Disease progression, intolerable toxicity most probably attributable to vismodegib, consent withdrawal, death, study termination by the Sponsor, or other reason deemed by the Investigator. vismodegib: 150 mg once daily until disease progression or unacceptable toxicity | Drug: vismodegib<br>* 150 mg once daily until disease progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Any Adverse Events (AEs), AEs Grade 3 or 4, AEs Leading to Drug Interruptions or Discontinuations and Any Serious Adverse Events (SAEs) | Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Percentage of Participants Who Died Due to Adverse Events, Disease Progression or Other Reasons | Reasons for other included unknown, natural causes, cardiac decompensation, general state alteration, deterioration of general state, clinical deterioration taking into consideration patient's age, old age, and disease progression of mediastinal squamous cell carcinoma (SCC). | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Percentage of Participants Who Report a Shift in NCI CTCAE Grades to 3/4 in Hematology and Biochemistry Laboratory Parameters |  | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Exposure to Study Treatment: Duration on Treatment | Duration on treatment was the number of days between first and last dose of study treatment. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Exposure to Study Treatment - Dose Intensity | Dose intensity was defined as the percentage of actual number of doses received versus planned. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate (BORR) | BORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) required a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Duration of Response | Duration of response was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of disease progression or death for any cause. Median duration of response was estimated using Kaplan-Meier estimates. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Time to Response | Time to response was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occur first). | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Progression-Free Survival (PFS) | PFS was defined as the time interval between the date of the first therapy and the date of progression or death for any causes, whichever occurs first. Disease progression was assessed by the investigator. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Overall Survival (OS) | OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. | Baseline to the data cut-off of 14 June 2017 (up to 6 years) | 
| Change From Baseline Scores of Skindex-16 Questionnaire Domains of Emotion, Function and Symptom | The Skindex-16 questionnaire includes three domains for the assessment of the effects of skin disease on participants' quality of life: symptoms, emotions and function. For each domain, responses from the questionnaire were transformed to a linear scale of 100 varying from 0 (never bothered, i.e., best) to 100 (always bothers, i.e., worst). | Baseline to the data cut-off date of 14 June 2017 (up to 6 years). | 
| Percentage of Participants With a ≥ 30% Reduction in Disease-Related Symptoms According to MDASI Scale | M.D. Anderson Symptom Inventory (MDASI) scale. The MDASI core instrument is a 19-item patient self-report questionnaire whose items comprise two scales, symptom severity and symptom interference. For 13 items (i.e., pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness or tingling), participants were asked to rate how severe the symptoms were when at their worst in the last 24 hours. For the remaining 6 items, participants were asked to rate how much the symptoms have interfered with 6 areas of functioning (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. | 08-May-2013 (Protocol Version ≥ 4) to the data cut-off date of 14 June 2017 (approximately 4 years and 1 month). | 
| Percentage of Participants With a ≥ 30% Reduction in Composite Symptom Severity Score According to MDASI Scale | M.D. Anderson Symptom Inventory (MDASI) scale. The MDASI core instrument is a 19-item patient self-report questionnaire whose items comprise two scales, symptom severity and symptom interference. For 13 items (i.e., pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness or tingling), participants were asked to rate how severe the symptoms were when at their worst in the last 24 hours. For the remaining 6 items, participants were asked to rate how much the symptoms have interfered with 6 areas of functioning (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. | 08-May-2013 (Protocol Version ≥ 4) to the data cut-off date of 14 June 2017 (approximately 4 years and 1 month). |