A Study of Two Vismodegib Regimens in Participants With Multiple Basal Cell Carcinomas

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, regimen-controlled, phase II, multicenter study will assess the efficacy and safety of two different vismodegib regimens in participants with multiple basal cell carcinoma. Participants will receive vismodegib 150 mg orally once daily either in an intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo (Arm A) or as 24 weeks induction followed by an intermittent schedule of 8 weeks placebo followed by 8 weeks vismodegib (Arm B). Anticipated time on study treatment is 72 weeks.

Official Title
-----------------
A Randomized, Double-blinded, Regimen-controlled, Phase II, Multicenter Study to Assess the Efficacy and Safety of Two Different Vismodegib Regimens in Patients With Multiple Basal Cell Carcinomas

Conditions
-----------------
Basal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Vismodegib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult participants, >/= 18 years of age Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least 6 clinically evident basal cell carcinomas at the time of randomization, of which 3 measure 5 mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions Histopathologic confirmation that at least one of the three target lesions is basal cell carcinoma Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Adequate renal and hepatic function and hematopoietic capacity Women of childbearing potential must agree to use contraception as defined by protocol during treatment and for at least 9 months after completion of study treatment Male participants with female partners of childbearing potential must agree to use contraception as defined by protocol during treatment and for 2 months after completion of study treatment Exclusion Criteria: Inability or unwillingness to swallow capsules Pregnant or breastfeeding women Any metastatic basal cell carcinoma Locally advanced basal cell carcinoma lesion that is considered to be inoperable or to have medical contraindications to surgery Recent (i.e., within the past 28 days prior to randomization) or current participation in another experimental drug study Known or suspected alcohol abuse One of the following known rare hereditary conditions: galactose intolerance, primary hypolactasia or glucose-galactose malabsorption

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vismodegib Intermittent Schedule<br>Vismodegib intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo, repeated 3 times with a final course of vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up | Drug: Vismodegib<br>* Vismodegib 150 mg hard gelatin capsule orally once daily<br>* Other names: Erivedge®;Drug: Placebo<br>* Vismodegib placebo orally once daily<br>|
| Experimental: Vismodegib Induction Followed by Intermittent Schedule<br>Vismodegib beginning with 24 weeks induction followed by intermittent schedule 8 weeks placebo, 8 weeks vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up | Drug: Vismodegib<br>* Vismodegib 150 mg hard gelatin capsule orally once daily<br>* Other names: Erivedge®;Drug: Placebo<br>* Vismodegib placebo orally once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment) | The total number of clinically evident basal cell carcinomas = the total number of target and/or non-target lesions present in individual participants. | Baseline; Week 73 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their symptoms, and their answers were combined into a composite Symptom Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). | Baseline; Week 73 | 
| Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their emotional state, and their answers were combined into a composite Emotion Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). | Baseline; Week 73 | 
| Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their ability to function, and answers were combined into a composite Function Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). | Baseline; Week 73 | 
| Percentage of Participants Experiencing Any Adverse Event |  | Up to 125 weeks | 
| Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | The percentage of participants who discontinued study treatment (due either to adverse event, refusal of treatment, or withdrawal of consent) was summarized by treatment group. | Baseline to Week 73 | 
| Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73 | The three target basal cell carcinoma lesions = the three largest visible lesions, at least 5 mm in the longest diameter, in individual participants. | Baseline; Week 73 | 
| Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73 |  | Baseline; Week 73 | 
| Percentage of Participants With New Basal Cell Carcinomas at Week 73 |  | Baseline; Week 73 | 
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate) |  | Baseline; Week 85 | 
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate) |  | Baseline; Week 97 | 
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate) |  | Baseline; Week 125 |