Basal Cell Carcinoma
Conditions
Brief summary
This randomized, double-blind, placebo-controlled study will assess the efficacy and safety of vismodegib with surgery in participants with basal cell carcinoma.
Interventions
DRUGPlacebo
Participants will receive matching placebo to vismodegib for 12 weeks.
DRUGVismodegib
Participants will receive vismodegib 150 mg oral capsule once a day for 12 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of non-infected, not recurrent, previously untreated basal cell carcinoma * Free of any significant physical abnormalities (e.g., tattoos) at the target basal cell carcinoma site * Willing and able to participate in the study as an outpatient and agreement to make frequent visits to the clinic during the treatment and follow-up periods and to comply with study requirements
Exclusion criteria
* Prior treatment with vismodegib * Known hypersensitivity to any of the study drug excipients * Any metastatic basal cell carcinoma * Any locally advanced basal cell carcinoma considered to be inoperable or to have a medical contraindication to surgery * Evidence of clinically significant and unstable diseases or conditions (e.g., cardiovascular, immunosuppressive, hematologic) * Any dermatological disease at the target basal cell carcinoma site that may cause difficulty with examination * Recent, current, or planned participation in another experimental drug study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Target Basal Cell Carcinoma (BCC) Expected Surgical Defect Area at Mohs Micrographic Surgery (MMS) Visit | Baseline, MMS visit (Week 12-14) | The percent change in target BCC expected surgical defect area was defined as (\[baseline expected surgical defect area - expected surgical defect area at MMS visit\]/ baseline expected surgical defect area) × 100 percent (%) where expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Actual Change in Target BCC Expected Surgical Defect Area at MMS Visit | Baseline, MSS Visit (Week 12-14) | Actual change was defined as (baseline expected surgical defect area - expected surgical defect area at MMS visit). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment. Expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry). |
| Percentage Change in Target BCC Actual Tumor-Free Margin Excision Area at MMS Visit | Baseline, MMS visit (Week 12-14) | Percent change in target BCC actual tumor-free margin excision area was defined as = (expected surgical defect area pre-treatment - actual tumor-free margin excision area at MMS visit) / expected surgical defect area pre-treatment) \* 100%. The actual tumor-free margin excision area (includes 2 millimeters \[mm\] margin) was measured during MMS. The area was photographed and traced on the digital photograph then calculated by computer-aided planimetry. MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment. |
| Percentage of Participants With Clinical Response | MMS visit (Week 12-14) | Clinical response was defined as a complete response (CR) or partial response (PR) at the post-treatment MMS excision. CR was defined as no histological evidence of BCC. PR was defined as a reduction of at least 50 % in the expected surgical defect area with histologic evidence of residual BCC. MMS visit was defined the visit that occurred within 2 weeks of the last study treatment. |
| Percentage of Participants With Skip Area | MMS visit (Week 12-14) | Skip area was defined as the presence of non-contiguous residual tumor at the MMS visit, as determined by an independent dermatopathologist. MMS visit occurred within 2 weeks of the last study treatment. |
| Percentage of Participants With BCC Recurrence | Baseline, 12, 24, and 52 weeks post MMS Visit (MMS Visit = Week 12-14) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vismodegib Participants received vismodegib 150 mg capsule orally once daily for 12 weeks. | 11 |
| Placebo Participants received matching placebo to vismodegib capsule orally once daily for 12 weeks. | 5 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Vismodegib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 10.87 | 73.6 years STANDARD_DEVIATION 7.27 | 72.2 years STANDARD_DEVIATION 9.68 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 11 | 2 / 5 |
| serious Total, serious adverse events | 3 / 11 | 0 / 5 |
Outcome results
Primary
Percent Change in Target Basal Cell Carcinoma (BCC) Expected Surgical Defect Area at Mohs Micrographic Surgery (MMS) Visit
The percent change in target BCC expected surgical defect area was defined as (\[baseline expected surgical defect area - expected surgical defect area at MMS visit\]/ baseline expected surgical defect area) × 100 percent (%) where expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment.
Time frame: Baseline, MMS visit (Week 12-14)
Population: ITT population. Here 'Number of participants analyzed' represents participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib | Percent Change in Target Basal Cell Carcinoma (BCC) Expected Surgical Defect Area at Mohs Micrographic Surgery (MMS) Visit | 31.52 Percent change in surgical defect area | Standard Deviation 35.58 |
| Placebo | Percent Change in Target Basal Cell Carcinoma (BCC) Expected Surgical Defect Area at Mohs Micrographic Surgery (MMS) Visit | 46.30 Percent change in surgical defect area | Standard Deviation 20.232 |
Secondary
Actual Change in Target BCC Expected Surgical Defect Area at MMS Visit
Actual change was defined as (baseline expected surgical defect area - expected surgical defect area at MMS visit). MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment. Expected surgical defect area was manually outlined on a digital photograph and measured by a computer (computer aided planimetry).
Time frame: Baseline, MSS Visit (Week 12-14)
Population: ITT Population. Here 'Number of participants analyzed' represents participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib | Actual Change in Target BCC Expected Surgical Defect Area at MMS Visit | 70.16 Square millimeter (mm^2) | Standard Deviation 82.483 |
| Placebo | Actual Change in Target BCC Expected Surgical Defect Area at MMS Visit | 93.33 Square millimeter (mm^2) | Standard Deviation 35.768 |
Secondary
Percentage Change in Target BCC Actual Tumor-Free Margin Excision Area at MMS Visit
Percent change in target BCC actual tumor-free margin excision area was defined as = (expected surgical defect area pre-treatment - actual tumor-free margin excision area at MMS visit) / expected surgical defect area pre-treatment) \* 100%. The actual tumor-free margin excision area (includes 2 millimeters \[mm\] margin) was measured during MMS. The area was photographed and traced on the digital photograph then calculated by computer-aided planimetry. MMS visit was defined as the visit that occurred within 2 weeks of the last study treatment.
Time frame: Baseline, MMS visit (Week 12-14)
Population: ITT. Here 'Number of participants analyzed' represents participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib | Percentage Change in Target BCC Actual Tumor-Free Margin Excision Area at MMS Visit | -12.24 Percent change in margin excision area | Standard Deviation 78.775 |
| Placebo | Percentage Change in Target BCC Actual Tumor-Free Margin Excision Area at MMS Visit | 25.29 Percent change in margin excision area | Standard Deviation 65.763 |
Secondary
Percentage of Participants With BCC Recurrence
Time frame: Baseline, 12, 24, and 52 weeks post MMS Visit (MMS Visit = Week 12-14)
Population: This outcome was based on the cumulative data post MMS Visit and due to early study termination with very few enrolled participants, complete data for this outcome measure could not be collected.
Secondary
Percentage of Participants With Clinical Response
Clinical response was defined as a complete response (CR) or partial response (PR) at the post-treatment MMS excision. CR was defined as no histological evidence of BCC. PR was defined as a reduction of at least 50 % in the expected surgical defect area with histologic evidence of residual BCC. MMS visit was defined the visit that occurred within 2 weeks of the last study treatment.
Time frame: MMS visit (Week 12-14)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vismodegib | Percentage of Participants With Clinical Response | 18.2 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Response | 40.0 Percentage of participants |
Comparison: The 95 % confidence interval (CI) for the difference in response rates was computed using the exact unconditional confidence limits method.95% CI: [-71.6, 32.1]
Secondary
Percentage of Participants With Skip Area
Skip area was defined as the presence of non-contiguous residual tumor at the MMS visit, as determined by an independent dermatopathologist. MMS visit occurred within 2 weeks of the last study treatment.
Time frame: MMS visit (Week 12-14)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vismodegib | Percentage of Participants With Skip Area | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Skip Area | 40.0 Percentage of participants |
95% CI: [-85.3, 14.2]