Vismodegib in Treating Patients With Basal Cell Carcinoma (BCC)

• ClinicalTrials.gov Identifier: NCT01631331
• Recruitment Status: Completed
• First Posted: June 29, 2012
• Results First Posted: October 2, 2017
• Last Update Posted: December 8, 2017
• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI); University Hospitals Cleveland Medical Center
• Information provided by (Responsible Party): Jean Yuh Tang, Stanford University

Tracking Information

• First Submitted Date: June 25, 2012
• First Posted Date: June 29, 2012
• Results First Submitted Date: February 2, 2017
• Results First Posted Date: October 2, 2017
• Last Update Posted Date: December 8, 2017
• Study Start Date: June 2012
• Actual Primary Completion Date: September 17, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 15, 2017)

Percent Change in Surgical Defect Area After the Treatment Period Using Calipers and Photographs Was Calculated [ Time Frame: 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.

Original Primary Outcome Measures (submitted: June 27, 2012)

Anti-tumor effect as measured by the percent change in surgical defect area against the null hypothesis of no change after the treatment period using calipers and photographs [ Time Frame: Baseline to 6 months ]

This will be tested against the null hypothesis of no change as a one-sample t-test. A p-value of less than 0.05 will be considered statistically significant. We will first perform non-parametric paired t-test taking this account, and also use more sophisticated methods such as the MIXED procedure (PROC MIXED) treating each subject as a random effect and time as fixed effect, with appropriate correlation structure.

Current Secondary Outcome Measures (submitted: August 15, 2017)

• Number of Tumors Demonstrating Histologic Cure [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 4 months (average) ]
  We measured the length and width of all tumors (target and non-target) before and after vismodegib treatment.

Original Secondary Outcome Measures (submitted: June 27, 2012)

• Proportion of tumors with skip lesions present determined using serial sectioning of tumor block and histology [ Time Frame: Assessed up to 6 months ]
• Average area of the subclinical tumor invasion calculated from the pre-surgical skin markings and by comparing the initial clinical margins to the final Mohs defect [ Time Frame: Assessed up to 6 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vismodegib in Treating Patients With Basal Cell Carcinoma (BCC)
• Official Title: A Pilot Study to Investigate the Off Label Use of Vismodegib as an Adjuvant to Surgery for Basal Cell Carcinoma Tumors (BCCs)
• 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.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Basal Cell Carcinoma of the Skin
• Recurrent Skin Cancer

Intervention

• Drug: vismodegib
  Given PO
  Other Names:

  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
• Procedure: Mohs surgery
  Undergo Mohs surgery

Study Arms

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.

Interventions:

• Drug: vismodegib
• Procedure: Mohs surgery

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 15, 2017): 15
• Original Estimated Enrollment (submitted: June 27, 2012): 20
• Actual Study Completion Date: May 31, 2016
• Actual Primary Completion Date: September 17, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01631331
• Other Study ID Numbers: IRB-24313; NCI-2012-01055 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); SKIN0012 ( Other Identifier: OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jean Yuh Tang, Stanford University
• Study Sponsor: Stanford University

Collaborators

• National Cancer Institute (NCI)
• University Hospitals Cleveland Medical Center

Investigators

• Principal Investigator: Jean Tang; Stanford University

• PRS Account: Stanford University
• Verification Date: August 2017