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

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.

Study Overview

• Status: Completed
• Conditions: Keratocystic Odontogenic Tumor
• Intervention / Treatment: Drug: vismodegib

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).

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10010
      • NYU Bluestone Center For Cllinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vismodegib; 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; 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.; 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)

Collaborators and Investigators

• Sponsor: NYU College of Dentistry
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Brian L Schmidt, DDS, MD, PhD, NYU College of Dentistry

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2015
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: February 5, 2015
• First Submitted That Met QC Criteria: February 18, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Keratocystic odontogenic tumor; KCOT
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Odontogenic Tumors
• Other Study ID Numbers: 15-00254; ML28859 (Other Identifier: Genentech)