Study Evaluating the Efficacy of Oral Vismodegib in Various Histologic Subtypes

NCT01700049 | Completed Phase 2 Results DMC

• 2 other identifiers: ML2848522355
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Basal Cell Carcinoma

Keywords

advanced BCC; high risk; locally advanced

Outcome Measures

Primary Outcomes (1)

• Efficacy of Vismodegib

  The efficacy of vismodegib was defined as the number of tumor biopsies with positive pathology after 24 weeks. Subjects had one target lesion and up to 3 additional non-target lesions. A cumulative total of 65 tumors was measured after 24 weeks of treatment. Histopathological subtypes were categorized primarily as infiltrative, nodular and superficial.

  Week 24

Secondary Outcomes (2)

• Safety of Vismodegib

  Up to 18 months

• Onset of Efficacy of Vismodegib

  Up to week 24

Study Arms (1)

Open Label oral vismodegib

EXPERIMENTAL

This is a Phase 2B single-site, open-label, nonrandomized 24-week study of the efficacy and safety of vismodegib (150 mg PO daily) in subjects with high risk and/or locally advanced basal cell carcinoma (BCC). A total of 36 subjects with infiltrative/morpheaform, nodular, or superficial BCC will be enrolled in the study.

Drug: vismodegib (150 mg PO daily)

Interventions

vismodegib (150 mg PO daily) DRUG

Biopsies will be performed on all participants at baseline, week 12 and week 24.

Also known as: Brand name: Erivedge

Open Label oral vismodegib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A signed and data informed consent
• Willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• years of age or older at time of informed consent
• Have 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
• or 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, and
• has been deemed not appropriate for radiation.
• Have a histologically-confirmed BCC prior to first dose of study drug
• Have 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Saint Louis University Department of Dermatology

St Louis, Missouri, 63104, United States

Location

Related Publications (5)

• Lorusso PM, Jimeno A, Dy G, Adjei A, Berlin J, Leichman L, Low JA, Colburn D, Chang I, Cheeti S, Jin JY, Graham RA. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2011 Sep 1;17(17):5774-82. doi: 10.1158/1078-0432.CCR-11-0972. Epub 2011 Jul 13.

  PMID: 21753154 BACKGROUND

• Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):389-402. doi: 10.1023/B:CANC.0000031775.04618.30.

  PMID: 15197337 BACKGROUND

• Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9. doi: 10.1056/NEJMoa1113713.

  PMID: 22670903 BACKGROUND

• Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH Jr. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012 Jun 7;366(23):2180-8. doi: 10.1056/NEJMoa1113538.

  PMID: 22670904 BACKGROUND

• Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.

  PMID: 19726763 BACKGROUND

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Carcinoma, Basal Cell

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell

Results Point of Contact

• Title: Dr. Scott Fosko
• Organization: Mayo Clinic

fosko.scott@mayo.edu

904-953-2303

Study Officials

• Scott Fosko, MD

  fosko.scott@mayo.edu

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 25, 2012
• First Posted: October 4, 2012
• Study Start: January 14, 2013
• Primary Completion: July 3, 2017
• Study Completion: July 3, 2018
• Last Updated: May 23, 2019
• Results First Posted: May 23, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)