A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors
Condition: Keratocystic Odontogenic Tumor
MeSH terms: Odontogenic Tumors
Intervention: vismodegib
Intervention description: vismodegib is a synthetic, small molecule inhibitor of the sonic Hh pathway, which is involved in tumorigenesis, thus providing a strong rationale for its use in the treatment of a variety of cancers.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Keratocystic odontogenic tumor; KCOT

Summary:

      The purpose of this study is to determine how well a daily dose of 150 mg of Erivedge
      (vismodegib) reduces Keratocystic odontogenic tumor (KCOT) size, and to evaluate the safety
      of this dose. Erivedge is FDA-approved for use in adults with a specific type of skin cancer.
      However, the drug is experimental for patients with KCOT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females, 18 years of age and above at the time the informed consent form is
             signed;

          -  Able to understand and sign the Informed Consent Form and other necessary paperwork
             prior to initiation of study procedures;

          -  Able to communicate with the investigator/study site personnel, understand and comply
             with the study requirements, and willing to return for specified visits at the
             appointed time;

          -  Patients who have received prior treatment for their KCOT and with a diagnosis of
             recurrent (maxillary or mandibular) sporadic KCOT or NBCCS-associated KCOT (single or
             multiple);

          -  Diagnosis of KCOT will be done by past pathology report or by biopsy at the study
             site, if applicable;

          -  Willingness to consent to biopsy of the lesion, if needed;

          -  Willingness to delay excision of the target tumor site, unless evidence of disease
             progression or lack of drug tolerability;

          -  Willingness to donate blood for genetic testing;

          -  For female patients of childbearing potential, agreement to use two acceptable methods
             of birth control, including one barrier method during the study and 7 months after
             discontinuation of study drug;

          -  For males with female partners of childbearing potential, agreement to use a male
             condom (with spermicide) and to advise their female partners to use an acceptable
             method of birth control during the study and for 2 months after the discontinuation of
             the study drug;

          -  Agreement not to donate blood/blood products during the study and for 7 months after
             the discontinuation of the study drug;

          -  For males not to donate sperm products or semen during treatment and for 2 months
             after the discontinuation of the study drug;

          -  Able and willing to swallow pill;

          -  No malabsorption syndrome or other condition that would interfere with enteral
             absorption;

          -  At least 4 weeks since last chemotherapy, investigational therapy, radiotherapy or
             major surgical procedure and recovered from the first study drug administration;

          -  KCOT measures at least 1 cm in one dimension on pretreatment volumetric CT scan;

          -  No clinically significant abnormalities with clinical laboratory assessments;

        Exclusion Criteria:

          -  Concurrent anti-tumor therapy;

          -  Completion of the most recent anti-tumor therapy (including Vismodegib) less than 4
             weeks prior to the initiation of treatment (first study drug administration);

          -  Uncontrolled medical illness;

          -  Pregnancy or lactation; female patients who are planning to become pregnant for the
             duration of the study and 7 months post-treatment;

          -  Inability or unwillingness to swallow capsules;

          -  Any medical or psychological illness or condition preventing adequate consent;

          -  History of significant atherosclerotic disease, including the following:

               -  Coronary artery disease (i.e., myocardial infarction within the past year or
                  unstable angina);

               -  Documented carotid atheroma;

          -  Known HIV infection;

          -  Current alcohol abuse;

          -  History of resistance to vismodegib (patients who previous received vismodegib for BCC
             and had no clinical response will be excluded).