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Study Evaluating the Efficacy of Oral Vismodegib in Various Histologic Subtypes

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by St. Louis University
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
St. Louis University
ClinicalTrials.gov Identifier:
NCT01700049
First received: September 25, 2012
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Basal Cell Carcinoma
Drug: vismodegib (150 mg PO daily)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ML28485:Phase 2B Single-site,Open-label,Nonrandomized Study Evaluating Efficacy of Oral Vismodegib in Various Histologic Subtypes (Infiltrative/Morpheaform,Nodular and Superficial)of High Risk and/or Locally Advanced Basal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by St. Louis University:

Primary Outcome Measures:
  • Efficacy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    Efficacy of vismodegib in treatment of target lesion(s) by clinical and histologic response evaluation.

    Clinical Response:

    • Comparison of # of target lesions in each group with overall response rate and best overall response rate
    • Comparison of maximum diameter and lesion area of target lesion(s) post-biopsy and at End of Treatment
    • Comparison of dimensions of tumor within "debulking" specimen at surgery visit with dimensions of pre-biopsy tumor

    Histologic response with evaluation of:

    • Residual tumor: Evidence of any histologic change in residual tumor tissue compared to pre-treatment biopsy specimens and estimate of changes in cellular density and composition
    • Area of Tumor Clearance with assessment of histologic clearance
    • Comparison of deepest "invasion index" on specimens
    • Histologic subtypes observed on pathologic specimens with location and depth of specific tumor cells
    • Percentage of each histologic subtype in tumor specimen on biopsy


Secondary Outcome Measures:
  • Safety [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]
    Safety and Tolerability Monitoring of adverse effects, onset of specific adverse effects and adverse effects that lead to early termination of treatment.

  • Onset of efficacy [ Time Frame: Up to week 24 ] [ Designated as safety issue: No ]

    Onset of efficacy during 24 weeks of treatment by clinical and histologic response

    o Histologic response measured at 12 weeks and after 24 weeks of treatment

    Interval to best overall response during 24 weeks of treatment by clinical response


  • Patient reported outcomes [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Patient Reported Outcomes/Quality of Life Evaluation of patient reported outcome (PRO) measures before, during 24 weeks of treatment with vismodegib through SKINDEX-16 and FACT-G questionnaires.


Estimated Enrollment: 36
Study Start Date: January 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label oral vismodegib
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. A total of 36 subjects with infiltrative/morpheaform, nodular, or superficial BCC will be enrolled in the study.
Drug: vismodegib (150 mg PO daily)
Biopsies will be performed on all participants at baseline, week 12 and week 24.
Other Name: Brand name: Erivedge

Detailed Description:

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. Each subtype has a characteristic look under the microscope, which is related to how the tumor will behave and grow. The histologic subtype can also help give your doctor information on how quickly your basal cell skin cancer will grow, if it will come back or if it will spread to other parts of your body.

ERIVEDGE (oral vismodegib capsule) has been approved for use in the United States for treatment of metastatic BCC tumors (mBCC), tumors that have spread further into the skin, bones or other tissues, or spread to other parts of the body and locally advanced basal cell skin cancer (laBCC), cancers that have come back after surgery or that the healthcare provider thinks cannot be treated with surgery or radiation. It works by blocking the signal, called Hedgehog, which basal cell skin cancer cells need to grow. It has been given to about 800 people during clinical trials.

Data from previous studies is mostly based on a subtype of BCC made up of little round collections of cancer cells, called "Nodular". There is almost no data on the use of vismodegib in other subtypes of BCC that that tend to extend deep into the skin ("Infiltrative" subtype), or spread widely near the surface of the skin ("Superficial" subtype). We know that the subtype of BCC 'can affect response to other types of treatment.

A total of 36 subjects will be enrolled in the study. All study participants will receive oral vismodegib treatment.

At the Week 12 visit, skin biopsies will be performed to give us more information on how your tumor is responding to vismodegib. If there is no evidence of tumor on the biopsy, you will be eligible to end treatment early and enter the Observation period. During this time you will be followed clinically every 3 months for up to 1 year.

For all other subjects, if any evidence of tumor is seen on biopsy at week 12, you will continue treatment for the full 24 weeks. At week 24 visit, skin biopsies will be performed again to see if there is any tumor left. If there is no evidence of tumor on the biopsy, you will be eligible to end treatment early and enter the Observation period. If there is tumor left, you will be referred for surgery or other standard of care treatment to remove the tumor.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. A signed and data informed consent
  2. Willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  3. 18 years of age or older at time of informed consent
  4. Have one or more clinically suspicious lesions for BCC at Pre-Study screening Visit that has:

    1. 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
    2. a diameter ≥ 10 mm if located on cheeks,forehead,scalp,or neck
    3. a diameter ≥ 20 mm if located on trunk and extremities

      or has a lesion suspicious for locally advanced BCC defined as a lesion that:

    4. is ≥ 10 mm,
    5. has recurred following surgery or surgical resection would result in substantial deformity, and
    6. has been deemed not appropriate for radiation.
  5. Have a histologically-confirmed BCC prior to first dose of study drug
  6. Have an Eastern Cooperative Oncology Group performance status of 2 or less at Baseline
  7. Female of reproductive potential must use 2 effective methods to avoid pregnancy during therapy and for 7 months after completing therapy
  8. 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
  9. Agree not to donate blood or blood products during the study and for 7 months after the last dose
  10. Subjects with Basal Cell Nevus Syndrome are eligible for enrollment

Exclusion Criteria:

  1. Women who are pregnant, lactating, or planning pregnancy while in the study
  2. History of prior treatment with vismodegib or any Hh Pathway Inhibitor
  3. Evidence of clinically significant and unstable diseases or conditions; Subjects with clinically stable chronic medical conditions will be allowed to enter the study
  4. Any dermatological disease at treatment site that the investigator thinks may be exacerbated by treatment with vismodegib or cause difficulty with examination
  5. 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
  6. Inability or unwillingness to swallow capsules
  7. 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
  8. History of infection requiring antimicrobial therapy within 2 wks prior to first dose of study drug
  9. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug
  10. Known to be infected with human immunodeficiency virus, hepatitis B or hepatitis C viruses
  11. 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
  12. 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
  13. Subjects who are study site staff members or who are Sponsor employees directly involved in the conduct of the trial
  14. A subject who, in the opinion of the investigator or sponsor, will be uncooperative or unable to comply with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700049

Contacts
Contact: Rosemary M King, PA-C, MPH 314-256-3454 dermresearch@slu.edu
Contact: Timur A Galperin, DO 314-256-3439 galperint@slu.edu

Locations
United States, Missouri
Saint Louis University Dermatology Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Timur A Galperin, DO    314-256-3439    galperint@slu.edu   
Contact: Rosemary M King, PA-C, MPH    314-256-3436    kingrm@slu.edu   
Sponsors and Collaborators
St. Louis University
Genentech, Inc.
Investigators
Principal Investigator: Scott W Fosko, MD Saint Louis University Dermatology
  More Information

Publications:
Responsible Party: St. Louis University
ClinicalTrials.gov Identifier: NCT01700049     History of Changes
Other Study ID Numbers: ML28485
Study First Received: September 25, 2012
Last Updated: October 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by St. Louis University:
advanced BCC
high risk
locally advanced

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Basal Cell
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Basal Cell
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2014