Vismodegib in Treating Patients With Basal Cell Carcinoma (BCC)

A Pilot Study to Investigate the Off Label Use of Vismodegib as an Adjuvant to Surgery for Basal Cell Carcinoma Tumors (BCCs)

The purpose of this study is to learn about the effect of vismodegib on sporadic basal cell carcinoma (BCCs) prior to surgical removal.

Study Overview

• Status: Completed
• Conditions: Recurrent Skin Cancer; Basal Cell Carcinoma of the Skin
• Intervention / Treatment: Drug: vismodegib; Procedure: Mohs surgery

Detailed Description

PRIMARY OBJECTIVES:

I. The percent reduction in surgical defect area/size surrounding BCC tumor pre and post-vismodegib.

SECONDARY OBJECTIVES:

I. Recurrence rate post treatment II. Safety, tolerability and percent drop-out after 3 vs. 6 months of vismodegib in otherwise healthy patients.

OUTLINE:

Patients receive vismodegib orally (PO) once daily (QD) for up to 3 months if the initial BCC size is < 2 cm and superficial or for up to 6 months if the initial BCC size is >= 2 cm or non-superficial. After completion of vismodegib treatment, patients undergo Mohs surgery.

After completion of study treatment, patients are followed up for an average of 24 months.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

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:

• Study patients must have at least one BCC, > 5 mm, eligible for Mohs surgical removal; patients with BCCs that have been treated before (recurrent BCCs, BCCs that failed other chemotherapy) are eligible for this trial, if they meet size criteria
• No Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status will be employed
• Normal hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x the upper limit of normal (ULN)
• Normal renal function : normal serum creatinine defined as <= 2.5 mg/dL
• Clinically acceptable complete blood count (CBC)
• Ability to understand and the willingness to sign a written informed consent document
• The patient is willing to forego surgical treatment of BCCs by up to 6 months, except when the principal investigator (PI) believes that delay in treatment potentially might compromise the health of the subject
• Documented negative serum pregnancy test for women of childbearing potential, with agreement to the use of two acceptable methods of contraception during the study and for 7 months after discontinuation of vismodegib
• For men with female partners of childbearing potential, agreement to use a latex, non-latex, or any other male condom and to advise their female partners to use an additional acceptable method of birth control during the study and for 2 months after discontinuation of study drug
• Be willing to not donate blood or semen for three months following discontinuation of study medications

Exclusion Criteria:

• The patient has a history of invasive cancer within the past five years excluding non-melanoma skin cancer, stage I cervical cancer, ductal carcinoma in situ of the breast, or chronic lymphocytic leukemia (CLL) stage 0

• The subject has uncontrolled systemic disease, including known human immunodeficiency virus (HIV) positive patients:

  • The patient has history of congestive heart failure
  • The patient has clinically important history of liver disease, including viral or hepatitis, current alcohol abuse, or cirrhosis
  • The patient has any condition or situation which in the investigator's opinion may put the patient at significant risk, could confound the study results, or could interfere significantly with the subject's participation in the study; this includes history of other skin conditions or disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications
• The patient has a history of hypersensitivity to any of the ingredients in the study medication formulations
• The patient is willing to abstain from application of non-study topical medications to the skin for the duration of the study, including prescription and over the counter preparations; for example, topical preparations containing corticosteroids or vitamin A derivatives are not allowed
• Pregnant or nursing patients will be excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (vismodegib and Mohs surgery); Patients receive vismodegib PO daily for 3-6 months based on the size of basal cell carcinoma and then undergo Mohs surgery.	Drug: vismodegib; Given PO; Other Names: Erivedge; GDC-0449; Hedgehog antagonist GDC-0449; Procedure: Mohs surgery; Undergo Mohs surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Surgical Defect Area After the Treatment Period Using Calipers and Photographs Was Calculated	At baseline, we selected 1 to 2 tumors per patient for surgery (13 target tumors selected). At baseline,1 Mohs surgeon measured the estimated surgical defect area around the target tumor. For tumors to be excised by Mohs we defined estimated surgical defect as the tumor size plus a 2-mm circumferential margin, presuming tumor clearance after a Mohs stage-1 excision. For the tumor undergoing standard (non-Mohs) excision, we used tumor size plus a standard 4-mm margin11 for the estimated surgical defect. On the day of the surgery, we measured the surgical defect area as the final tumor-free defect after the Mohs procedure or non-Mohs excision immediately before closure. We used the Image J software program (National Institutes of Health, Bethesda, MD) to calculate tumor area (cm2). Only target tumors are included in this analysis.	average of 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Tumors Demonstrating Histologic Cure	Determination of histologic cure (no residual BCC on the first piece of excised tissue) post serial sectioning of paraffin embedded Mohs specimens	Average of 4 months
Tumor Recurrence Rate of Treated BCCs	Recurrence rate of BCCs during a 22 month average (range 12 to 28 months) follow up period.	average of 22 months
Tumor Size Measurements Before and After Short Term Vismodegib Treatment	We measured the length and width of all tumors (target and non-target) before and after vismodegib treatment.	4 months (average)

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI); University Hospitals Cleveland Medical Center
• Investigators: Principal Investigator: Jean Tang, Stanford University

Publications and helpful links

General Publications

• Ally MS, Aasi S, Wysong A, Teng C, Anderson E, Bailey-Healy I, Oro A, Kim J, Chang AL, Tang JY. An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma. J Am Acad Dermatol. 2014 Nov;71(5):904-911.e1. doi: 10.1016/j.jaad.2014.05.020. Epub 2014 Jun 11.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): September 17, 2015
• Study Completion (ACTUAL): May 31, 2016

Study Registration Dates

• First Submitted: June 25, 2012
• First Submitted That Met QC Criteria: June 27, 2012
• First Posted (ESTIMATE): June 29, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 8, 2017
• Last Update Submitted That Met QC Criteria: November 6, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell
• Other Study ID Numbers: IRB-24313; NCI-2012-01055 (REGISTRY: CTRP (Clinical Trial Reporting Program)); SKIN0012 (OTHER: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No