Vismodegib in Treating Patients With Basal Cell Carcinoma (BCC)

Early Phase 1

Completed

Conditions: Basal Cell Carcinoma of the Skin
Recurrent Skin Cancer

Interventions: Drug: vismodegib
Procedure: Mohs surgery

Registration Number: NCT01631331

Lead Sponsor: Stanford University

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (vismodegib and Mohs surgery)	Mohs surgery	Patients receive vismodegib PO daily for 3-6 months based on the size of basal cell carcinoma and then undergo Mohs surgery.
Treatment (vismodegib and Mohs surgery)	vismodegib	Patients receive vismodegib PO daily for 3-6 months based on the size of basal cell carcinoma and then undergo Mohs surgery.

Primary Outcome Measures

Name	Time	Method
Percent Change in Surgical Defect Area After the Treatment Period Using Calipers and Photographs Was Calculated	average of 4 months	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.

Secondary Outcome Measures

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