Vismodegib for Treatment of Basal Cell Carcinoma
Condition: Basal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Basal Cell
Intervention: Vismodegib; Placebo
Intervention description: Oral vismodegib, 150mg per day for 12 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Basal Cell Carcinoma; Treatment of Skin Cancer

Summary:

      The primary objectives of this study are to assess, using Mohs micrographic surgery (MMS) at
      the end of treatment, the efficacy (primary) and safety (secondary) of vismodegib compared to
      placebo in the oral adjunctive pre surgical treatment of basal cell carcinoma. A secondary
      objective is to assess how often and in what types of lesions does pre surgical treatment
      with vismodegib result in complete eradication of the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Willing and able to give informed consent.

          2. At least 18 years of age.

          3. Have a confirmed BCC at one of listed anatomical sites which must be biopsy-confirmed
             at the study site and meets this criteria:

               -  non-infected

               -  minimum tumor area of 0.5 cm2 in an anatomic location at risk for significant
                  deformity or functional impairment with surgery.

               -  macroscopically (clinically) consistent with BCC

               -  histologically consistent with BCC

               -  suitable for treatment with Mohs surgical excision

               -  identifiable by subject or reliable subject representative

          4. Free of any significant physical abnormalities (e.g., tattoos) at treatment site.

          5. Willing and able to participate in the study as an outpatient, making frequent visits
             to clinic during treatment and follow-up periods and comply with study requirements,
             including:

               -  Consenting to biopsy of the lesion at baseline, if needed, before beginning study
                  drug treatment

               -  Attend all scheduled clinic visits during pre-study, treatment, and follow-up
                  periods

               -  Will delay excision of the target tumor site until time mandated in the protocol,
                  unless evidence of disease progression or lack of drug tolerability

               -  Post-excisional follow-up visits until the area is healed to investigator's
                  satisfaction

          6. Female of reproductive potential must use 2 forms of acceptable contraception
             (including one acceptable barrier method with spermicide) during therapy and for 7
             months after completing therapy.

          7. Male patients must use condoms at all times, with spermicide, even after vasectomy,
             during sexual intercourse with females during treatment and for 2 months after the
             last dose.

          8. Agrees not to donate blood or blood products during the study and for 7 months after
             last dose.

        Exclusion Criteria:

          1. Prior treatment with GDC-0449 or any HH Pathway Inhibitor

          2. Have evidence of clinically significant, unstable cardiovascular or immunosuppressive,
             hematologic, hepatic, neurologic, renal, endocrine, collagen-vascular, or
             gastrointestinal abnormalities or disease. Subjects with clinically stable medical
             conditions including, but not limited to, controlled hypertension, diabetes mellitus
             type II, hypercholesterolemia, or osteoarthritis, will be allowed to enter the study.

          3. Have any dermatological disease at treatment site that may be exacerbated by treatment
             with vismodegib or cause difficulty with examination (e.g., psoriasis, eczema).

          4. Inability or unwillingness to swallow capsules

          5. Pregnancy or lactation

          6. Have a desire to conceive in the future.

          7. Patients with known Gorlin's (basal cell nevus) syndrome or clinical suspicion of
             Gorlin's Syndrome)

          8. Recent (i.e., within the past 28 days), current, or planned participation in another
             experimental drug study

          9. Have active chemical dependency or alcoholism..

         10. Have received following treatments for BCC in the treatment area within designated
             time period before study treatment initiation:

             Treatment Time Period:

             Prescribed topical retinoids 4 weeks Surgical excision 4 weeks Curettage 4 weeks Cryo
             destruction or chemo destruction 4 weeks

         11. Received treatment for non-melanoma skin cancer or precancerous condition [squamous
             cell carcinoma (SCC), or actinic keratosis (AK)] within treatment area within 4 weeks
             of study treatment initiation, or currently have SCC, malignant melanoma (MM), or any
             other dermatological condition in treatment area that requires treatment.

         12. Received any cancer chemotherapy within 6 months before study treatment initiation
             (subject must not currently have any evidence of cancer, other than skin cancer).

         13. Received any of the following treatments within 4 weeks before study treatment
             initiation:

               -  Interferon or interferon inducers

               -  Immunomodulators or immunosuppressive therapies

               -  Cytotoxic drugs

               -  Investigational drugs

               -  Drugs known to have major organ toxicity

               -  Oral corticosteroids

               -  Inhaled corticosteroids (> 1200 Xg/day for beclomethasone, or > 600 Xg/day for
                  fluticasone)

               -  Topical steroids in treatment area