a phase 2, single-center, single-arm, open label trial of vismodegib in patients with keratocystic odontogenic tumors

Conditions: Keratocystic Odontogenic Tumor

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.

this is a single-center, interventional, single-arm, open-label, two-cohort clinical trial. a total of 20 patients will be enrolled (10 with nbccs-associated kcot and 10 with sporadic kcot) over a period of 2 years. this is a 3 year study where each patient will undergo up to 1 year of treatment and up to 2 years of post-treatment follow-up. all patients will be assessed for safety and efficacy of the study drug gdc-0449 (vismodegib).

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).

Keywords: keratocystic odontogenic tumor kcot