Study Evaluating the Efficacy of Oral Vismodegib in Various Histologic Subtypes
|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|
- 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.
- 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
- 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.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700049
|Contact: Rosemary M King, PA-C, MPHemail@example.com|
|Contact: Joseph Kallini, MDfirstname.lastname@example.org|
|United States, Missouri|
|Saint Louis University Dermatology||Recruiting|
|Saint Louis, Missouri, United States, 63104|
|Contact: Joseph Kallini, MD 314-256-3407 email@example.com|
|Contact: Rosemary M King, PA-C, MPH 314-256-3436 firstname.lastname@example.org|
|Principal Investigator:||Scott W Fosko, MD||Saint Louis University Dermatology|