A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449) in Operable Basal Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
This was a 3-cohort, open-label study of vismodegib (GDC-0449) in new (non-recurrent) operable basal cell carcinoma of the nodular subtype.

Detailed Description
-----------------
For Cohort 1, the response to treatment was determined at the end of the 12 weeks of treatment. For Cohort 2, the response to treatment was determined after 12 weeks of treatment and 24 weeks of observation. For Cohort 3, the response to treatment was determined after intermittent dosing over a 20-week period, consisting of an initial 8-week treatment period, followed by a 4-week drug holiday period, followed by a second 8-week treatment period.

Official Title
-----------------
A Phase II, Multicenter, Open-label, Three-cohort Trial Evaluating the Efficacy and Safety of Vismodegib (GDC-0449) in Operable Basal Cell Carcinoma (BCC)

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed new (not recurrent or previously treated) nodular basal cell carcinoma (BCC) at 1 of the listed anatomical sites, which must be biopsy confirmed at the study site. Willingness to consent to biopsy of the lesion. Willingness to delay excision of the target tumor site until the time mandated in the protocol, unless evidence of disease progression or lack of drug tolerability. Adequate hematopoietic capacity. Adequate hepatic function. For women of childbearing potential, agreement to use 2 acceptable forms of birth control (including one barrier method) during the study and for 7 months after discontinuation of study drug. For men with female partners of childbearing potential, agreement to use a male condom (with spermicide) and to advise their female partners to use an additional acceptable method of birth control during the study and for 2 months after discontinuation of study drug. Agreement not to donate blood/blood products during the study and for 7 months after discontinuing study drug. Agreement not to donate sperm or semen during treatment and for 2 months after the last dose of vismodegib. Exclusion Criteria: Prior treatment with vismodegib or any Hedgehog pathway inhibitor. Inability or unwillingness to swallow capsules. Pregnancy or lactation. BCC with any clinical and histological pattern other than nodular BCC. Patients with known Gorlin's syndrome (basal cell nevus syndrome) or clinical suspicion of Gorlin's syndrome. Recent (ie, within the past 28 days), current, or planned participation in another experimental drug study. Use of any excluded medication or therapy within 21 days of study entry. History of other malignancies within 3 years of the first day of treatment (Day 1), except for tumors with a negligible risk of metastasis, such as other non-melanoma skin cancer (BCC, squamous cell cancer), ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix. Uncontrolled medical illness. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications. Any medical or psychological illness or condition preventing adequate consent.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Vismodegib 150 mg<br>Participants received vismodegib 150 mg orally daily for 12 weeks. | Drug: Vismodegib<br>* Vismodegib was supplied in gelatin capsules.<br>* Other names: GDC-0449;|
| Experimental: Cohort 2: Vismodegib 150 mg<br>Participants received vismodegib 150 mg orally daily for 12 weeks. | Drug: Vismodegib<br>* Vismodegib was supplied in gelatin capsules.<br>* Other names: GDC-0449;|
| Experimental: Cohort 3: Vismodegib 150 mg<br>Participants received vismodegib 150 mg orally daily for 8 weeks, followed by 4 weeks with no treatment, followed by a second 8-week vismodegib treatment period. | Drug: Vismodegib<br>* Vismodegib was supplied in gelatin capsules.<br>* Other names: GDC-0449;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Histologic Clearance | Complete histologic clearance was defined as the absence of histological evidence of basal cell carcinoma at the target tumor site. Histological examination was performed by an independent pathologist on specimens collected within 2 weeks of the end of treatment period, ie, at 12 weeks after Baseline in Cohort 1, at 36 weeks after Baseline in Cohort 2, and at 20 weeks after Baseline in Cohort 3. | Baseline to Week 12 (Cohort 1), Baseline to Week 36 (Cohort 2), Baseline to Week 20 (Cohort 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Complete Clinical Clearance | Time to complete clinical clearance was defined as the time from the first treatment with vismodegib until complete clinical clearance as determined by the investigator. | Baseline to the end of the study (up to 12 weeks for Cohort 1; up to 36 weeks for Cohort 2, up to 20 weeks for Cohort 3) |