Keratocystic Odontogenic Tumor
Conditions
Keywords
Keratocystic odontogenic tumor, KCOT
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).
Interventions
DRUGvismodegib
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.
Sponsors
Genentech, Inc.
NYU College of Dentistry
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| KCOT Volume (Greatest Dimension) | Baseline, 6 month (in treatment), 1 year (in treatment), 2 Year (post-treatment), 3 Year (post-treatment) | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at the NYU Oral cancer center between mmyy and mmyy. The first participant was enrolled in mmyy and the last subject was enrolled in mmyy.
Pre-assignment details
Of 3 enrolled subjects, 2 met inclusion criteria and received treatment.
Participants by arm
| Arm | Count |
|---|---|
| NBCCS-associated KCOT Nevoid Basal Cell Carcinoma Syndrome (NBCCS)-associated Keratocystic Odontogenic Tumor (KCOT) Group | 1 |
| Sporadic KCOT Sporadic Keratocystic Odontogenic Tumor (KCOT) Group | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | NBCCS-associated KCOT | Sporadic KCOT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Primary KCOT Tumor size at Baseline | 3 centimeter | 3.8 centimeter | 2 centimeter |
| Race/Ethnicity, Customized African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 |
Outcome results
Primary
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.
Time frame: Baseline, 6 month (in treatment), 1 year (in treatment), 2 Year (post-treatment), 3 Year (post-treatment)
Population: Subjects received ERIVEDGE® (vismodegib) 150 mg capsule orally once daily for 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NBCCS-associated KCOT | KCOT Volume (Greatest Dimension) | 1 Year (In treatment) | 2.3 centimeter |
| NBCCS-associated KCOT | KCOT Volume (Greatest Dimension) | 6 month (In treatment) | 0 centimeter |
| NBCCS-associated KCOT | KCOT Volume (Greatest Dimension) | 2 Year (post-treatment) | 2.2 centimeter |
| NBCCS-associated KCOT | KCOT Volume (Greatest Dimension) | 3 Year (post-treatment) | 2.0 centimeter |
| NBCCS-associated KCOT | KCOT Volume (Greatest Dimension) | Baseline | 3 centimeter |
| Sporadic KCOT | KCOT Volume (Greatest Dimension) | 3 Year (post-treatment) | 0 centimeter |
| Sporadic KCOT | KCOT Volume (Greatest Dimension) | Baseline | 3.8 centimeter |
| Sporadic KCOT | KCOT Volume (Greatest Dimension) | 6 month (In treatment) | 2.6 centimeter |
| Sporadic KCOT | KCOT Volume (Greatest Dimension) | 1 Year (In treatment) | 2.0 centimeter |
| Sporadic KCOT | KCOT Volume (Greatest Dimension) | 2 Year (post-treatment) | 1.9 centimeter |