Basal Cell Carcinoma
Conditions
Keywords
advanced BCC, high risk, locally advanced
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.
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. 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). 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 the investigators more information on how the tumor is responding to vismodegib. If there is no evidence of tumor on the biopsy, the subject will be eligible to end treatment early and enter the Observation period. During this time the subject 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, the subject 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, the subject will be eligible to end treatment early and enter the Observation period. If there is tumor left, the subject will be referred for surgery or other standard of care treatment to remove the tumor.
Interventions
DRUGvismodegib (150 mg PO daily)
Biopsies will be performed on all participants at baseline, week 12 and week 24.
Sponsors
Genentech, Inc.
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Vismodegib | Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Vismodegib | Up to 18 months | The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death. |
| Onset of Efficacy of Vismodegib | Up to week 24 | Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
vismodegib (150 mg PO daily): Biopsies will be performed on all participants at baseline, week 12 and week 24. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Open Label Oral Vismodegib |
|---|---|
| Age, Continuous | 69.5 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 4 / 28 |
Outcome results
Primary
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.
Time frame: Week 24
Population: A total of 65 tumors were categorized into histopathologic subtype where 24 of 65 were infiltrative, 29 of 65 were nodular, 10 of 65 were superficial and 2 out of 65 were keratotic.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Open Label Oral Vismodegib | Efficacy of Vismodegib | Keratotic | 1 tumors |
| Open Label Oral Vismodegib | Efficacy of Vismodegib | Infiltrative | 2 tumors |
| Open Label Oral Vismodegib | Efficacy of Vismodegib | Nodular | 5 tumors |
| Open Label Oral Vismodegib | Efficacy of Vismodegib | Superficial | 1 tumors |
Secondary
Onset of Efficacy of Vismodegib
Onset of efficacy was measured by tumor surface area reduction or increase. Subjects had one target lesion and up to 3 additional non-target lesions. Surface area of a cumulative total of 65 tumors (27 target lesions and 38 non-target lesions) was measured after 24 weeks of treatment. A complete response was defined as 100% reduction in tumor surface area. Partial response was defined as greater than 50% reduction in tumor surface area. Stable disease was defined as less than 50% reduction in tumor surface area and Progressive disease was defined as greater than 20% increase in tumor surface area.
Time frame: Up to week 24
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Open Label Oral Vismodegib | Onset of Efficacy of Vismodegib | Complete response | 13 tumors |
| Open Label Oral Vismodegib | Onset of Efficacy of Vismodegib | Partial response | 27 tumors |
| Open Label Oral Vismodegib | Onset of Efficacy of Vismodegib | Stable Disease | 24 tumors |
| Open Label Oral Vismodegib | Onset of Efficacy of Vismodegib | Progressive Disease | 1 tumors |
Secondary
Safety of Vismodegib
The safety of Vismodegib was evaluated by monitoring adverse effects. All adverse events, expected and unexpected, were recorded and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) guide. This is a set of criteria from the National Cancer Institute (NCI) used to standardize classification of adverse effects of drugs. Grade 1 events are defined as mild, grade 2 as moderate, grade 3 as severe; grade 4 as life-threatening and grade 5 as death.
Time frame: Up to 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label Oral Vismodegib | Safety of Vismodegib | Grade 3 | 8 adverse events |
| Open Label Oral Vismodegib | Safety of Vismodegib | Grade 4 | 1 adverse events |
| Open Label Oral Vismodegib | Safety of Vismodegib | Grade 5 | 2 adverse events |
| Open Label Oral Vismodegib | Safety of Vismodegib | Grade 1 | 133 adverse events |
| Open Label Oral Vismodegib | Safety of Vismodegib | Grade 2 | 48 adverse events |