A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors

Study Overview
=================
Brief 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.

Detailed Description
-----------------
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).

Official Title
-----------------
A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors

Conditions
-----------------
Keratocystic Odontogenic Tumor

Intervention / Treatment
-----------------
* Drug: vismodegib


Participation Criteria
=================
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).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vismodegib<br>The 150-mg vismodegib drug product is a hard gelatin capsule formulation for oral administration. This study involves one year of treatment with Erivedge (150 mg/day) plus two years of follow-up. | Drug: vismodegib<br>* 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.<br>* Other names: ERIVEDGE®, GDC-0449;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| KCOT Volume (Greatest Dimension) | To evaluate the efficacy of GDC-0449 in reducing KCOT size (shrinkage) in NBCCS-associated KCOT and sporadic KCOT patients following 6 to 12 months of ingestion of 150 mg/day, up to 1 year of treatment and up to 2 years of post- treatment follow-up. | Baseline, 6 month (in treatment), 1 year (in treatment), 2 Year (post-treatment), 3 Year (post-treatment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Keratocystic odontogenic tumor, KCOT