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

• Sponsor: NYU College of Dentistry (Other)
• Overall Status: Completed
• CT.gov ID: NCT02366312
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 45.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Keratocystic Odontogenic Tumor	Drug: vismodegib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors
• Actual Study Start Date: Oct 27, 2015
• Actual Primary Completion Date: Aug 1, 2019
• Actual Study Completion Date: Aug 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Bluestone Center For Cllinical Research	New York	New York	United States	10010

Sponsors and Collaborators

• NYU College of Dentistry
• Genentech, Inc.

Investigators

• Principal Investigator: Brian L Schmidt, DDS, MD, PhD, NYU College of Dentistry

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 14, 2016
• Informed Consent Form - Oct 20, 2016

More Information

Publications

None provided.

• Responsible Party: Brian L. Schmidt, Director, Bluestone Center for Clinical Research, NYU College of Dentistry
• ClinicalTrials.gov Identifier: NCT02366312
• Other Study ID Numbers: 15-00254; ML28859
• First Posted: Feb 19, 2015
• Last Update Posted: Feb 18, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Brian L. Schmidt, Director, Bluestone Center for Clinical Research, NYU College of Dentistry: Keratocystic odontogenic tumor; KCOT
• Additional relevant MeSH terms: Odontogenic Tumors

Study Results

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 Detail	Of 3 enrolled subjects, 2 met inclusion criteria and received treatment.

Arm/Group Title	NBCCS-associated KCOT	Sporadic KCOT
Arm/Group Description	Nevoid Basal Cell Carcinoma Syndrome (NBCCS)-associated Keratocystic Odontogenic Tumor (KCOT) Group	Sporadic Keratocystic Odontogenic Tumor (KCOT) Group
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	0
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	NBCCS-associated KCOT	Sporadic KCOT	Total
Arm/Group Description	Nevoid Basal Cell Carcinoma Syndrome (NBCCS)-associated Keratocystic Odontogenic Tumor (KCOT) Group	Sporadic Keratocystic Odontogenic Tumor (KCOT) Group	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Race/Ethnicity, Customized (Count of Participants)
White - Not Hispanic or Latino	1 100%	0 0%	1 50%
Hispanic or Latino	0 0%	1 100%	1 50%
African American	0 0%	0 0%	0 0%
Asian/Pacific Islander	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%
Primary KCOT Tumor size at Baseline (centimeter) [Number]
Number [centimeter]	3	3.8	2

Outcome Measures

1. Primary Outcome

Title	KCOT Volume (Greatest Dimension)
Description	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)

Outcome Measure Data

Analysis Population Description

Subjects received ERIVEDGE® (vismodegib) 150 mg capsule orally once daily for 12 months.

Arm/Group Title	NBCCS-associated KCOT	Sporadic KCOT
Arm/Group Description	Nevoid Basal Cell Carcinoma Syndrome (NBCCS)-associated Keratocystic Odontogenic Tumor (KCOT) Group	Sporadic Keratocystic Odontogenic Tumor (KCOT) Group
Measure Participants	1	1
Baseline	3	3.8
6 month (In treatment)	0	2.6
1 Year (In treatment)	2.3	2.0
2 Year (post-treatment)	2.2	1.9
3 Year (post-treatment)	2.0	0

Adverse Events

Time Frame	Up to three years
Arm/Group Title	NBCCS-associated KCOT		Sporadic KCOT
Arm/Group Description	Nevoid Basal Cell Carcinoma Syndrome (NBCCS)-associated Keratocystic Odontogenic Tumor (KCOT) Group		Sporadic Keratocystic Odontogenic Tumor (KCOT) Group
All Cause Mortality
	NBCCS-associated KCOT		Sporadic KCOT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	NBCCS-associated KCOT		Sporadic KCOT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)
Blood and lymphatic system disorders
High grade Newuorendocrine Carcinoma of head/neck	0/1 (0%)	0	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	NBCCS-associated KCOT		Sporadic KCOT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Ear and labyrinth disorders
Earache	0/1 (0%)	0	1/1 (100%)	1
Endocrine disorders
bilateral lower extremities swelling	0/1 (0%)	0	1/1 (100%)	1
Gastrointestinal disorders
Pain	0/1 (0%)	0	1/1 (100%)	1
GI upset	1/1 (100%)	2	0/1 (0%)	0
Loose stool	1/1 (100%)	2	0/1 (0%)	0
General disorders
Pain	0/1 (0%)	0	1/1 (100%)	1
Sore Throat	0/1 (0%)	0	1/1 (100%)	1
Allergic reaction	1/1 (100%)	1	0/1 (0%)	0
Cold symptoms	1/1 (100%)	2	0/1 (0%)	0
Loss of taste	0/1 (0%)	0	1/1 (100%)	1
Infections and infestations
Nasopharyn lesion	0/1 (0%)	0	1/1 (100%)	1
Musculoskeletal and connective tissue disorders
Cramping	0/1 (0%)	0	1/1 (100%)	1
spasm	1/1 (100%)	1	0/1 (0%)	0
Spasm	1/1 (100%)	1	0/1 (0%)	0
cramp	1/1 (100%)	1	0/1 (0%)	0
Leg Cramp	1/1 (100%)	1	0/1 (0%)	0
Toes cramping	0/1 (0%)	0	1/1 (100%)	1
lower extremity pain	0/1 (0%)	0	1/1 (100%)	1
Right facial pain	0/1 (0%)	0	1/1 (100%)	1
Left sided muscle ache	1/1 (100%)	1	0/1 (0%)	0
Sacral injury	1/1 (100%)	1	0/1 (0%)	0
Nervous system disorders
Facial numbness	1/1 (100%)	1	0/1 (0%)	0
Headache	1/1 (100%)	1	0/1 (0%)	0
Reproductive system and breast disorders
Upper Respiratory Infection	1/1 (100%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chest Discomfort	1/1 (100%)	2	0/1 (0%)	0
Skin and subcutaneous tissue disorders
Hair loss	0/1 (0%)	0	1/1 (100%)	1

Limitations/Caveats

Enrollment for the study closed early by the sponsor due to low enrollment number. Only two subjects were enrolled and received the study treatment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.