A Study Evaluating the Effectiveness of Oral Vismodegib in Various Histologic Subtypes of High Risk or Locally Advanced Basal Cell Carcinoma

Overview

About this study

The purpose of this study is to investigate the safety and effectiveness of oral vismodegib therapy in the treatment of different 'histologic subtypes' of basal cell skin cancer (BCC). The term 'histologic subtype' refers to how the cells and tumor tissue looks under the microscope. Three different 'histologic subtypes' of basal cell skin cancer (infiltrative/morpheaform, nodular and superficial) will be examined in this study.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • A signed and data informed consent
  • Willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  • 18 years of age or older at time of informed consent
  • Has one or more clinically suspicious lesions for BCC at pre-study screening visit that has:
    • A diameter ≥ 6 mm if located on the "mask areas" of face (central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin/sulci,temple,ear),genitalia,hands,or feet
    • A diameter ≥ 10 mm if located on cheeks, forehead, scalp, or neck
    • A diameter ≥ 20 mm if located on trunk and extremities
  • Has a lesion suspicious for locally advanced BCC defined as a lesion that
    • Is ≥ 10 mm
    • Has recurred following surgery or surgical resection would result in substantial deformity
    • Has been deemed not appropriate for radiation
  • Has a histologically-confirmed BCC prior to first dose of study drug
  • Has an Eastern Cooperative Oncology Group performance status of 2 or less at baseline
  • Female of reproductive potential must use 2 effective methods to avoid pregnancy during therapy and for 7 months after completing therapy
  • Male patients must use effective measures to avoid pregnancy in their partner at all times during treatment and for 2 months after the last dose
  • Agree not to donate blood or blood products during the study and for 7 months after the last dose
  • Subjects with Basal Cell Nevus Syndrome are eligible for enrollment

Exclusion Criteria

  • Women who are pregnant, lactating, or planning pregnancy while in the study
  • History of prior treatment with vismodegib or any Hh Pathway Inhibitor
  • Evidence of clinically significant and unstable diseases or conditions
    • Subjects with clinically stable chronic medical conditions will be allowed to enter the study
  • Any dermatological disease at treatment site that the investigator thinks may be exacerbated by treatment with vismodegib or cause difficulty with examination
  • The target lesion identified at pre-study screening visit has been determined to be mBCC by radiological assessment prior to first dose of study drug
  • Inability or unwillingness to swallow capsules
  • History of infection requiring hospitalization, IV antimicrobial therapy, or is otherwise judged to be clinically significant by the investigator within 4 wks prior to first dose of study drug
  • History of infection requiring antimicrobial therapy within 2 wks prior to first dose of study drug
  • History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug
  • Known to be infected with human immunodeficiency virus, hepatitis B or hepatitis C viruses
  • Participation in other study using an investigational or experimental therapy or procedure within 4 weeks or 5 half-lives (whichever is longer) before the study begins and/or during study participation
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results in the judgment of the investigator
  • Subjects who are study site staff members or who are Sponsor employees directly involved in the conduct of the trial
  • A subject who, in the opinion of the investigator or sponsor, will be uncooperative or unable to comply with study procedures

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Scott Fosko, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

  • Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. Read More on PubMed
  • Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. Read More on PubMed
  • This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing. Read More on PubMed
  • Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma. In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug. Read More on PubMed
  • Basal cell carcinoma (BCC) is the most common cutaneous skin malignancy. BCC generally has a clinical course characterized by slow growth, minimal soft tissue invasiveness, and a high cure rate. Occasionally, however, BCC behaves aggressively with deep invasion, recurrence, and potential regional and distant metastasis. Several factors, including tumor size, duration, histology, and perineural spread, have been postulated as markers of the aggressive BCC phenotype. It is undetermined whether intrinsic biological factors within certain subsets of BCC predispose these tumors toward an inherently aggressive behavior, or whether any BCC with inadequate early management may assume this phenotype. Review of the pertinent literature on this topic suggests that both intrinsic biological factors and extrinsic management factors play a role in the development and progression of aggressive BCC. Read More on PubMed
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