Basal Cell Carcinoma
Conditions
Brief summary
This randomized, double-blind, regimen-controlled, phase II, multicenter study will assess the efficacy and safety of two different vismodegib regimens in participants with multiple basal cell carcinoma. Participants will receive vismodegib 150 mg orally once daily either in an intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo (Arm A) or as 24 weeks induction followed by an intermittent schedule of 8 weeks placebo followed by 8 weeks vismodegib (Arm B). Anticipated time on study treatment is 72 weeks.
Interventions
DRUGVismodegib
Vismodegib 150 mg hard gelatin capsule orally once daily
DRUGPlacebo
Vismodegib placebo orally once daily
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
* Adult participants, \>/= 18 years of age * Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least 6 clinically evident basal cell carcinomas at the time of randomization, of which 3 measure 5 mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions * Histopathologic confirmation that at least one of the three target lesions is basal cell carcinoma * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Adequate renal and hepatic function and hematopoietic capacity * Women of childbearing potential must agree to use contraception as defined by protocol during treatment and for at least 9 months after completion of study treatment * Male participants with female partners of childbearing potential must agree to use contraception as defined by protocol during treatment and for 2 months after completion of study treatment
Exclusion criteria
* Inability or unwillingness to swallow capsules * Pregnant or breastfeeding women * Any metastatic basal cell carcinoma * Locally advanced basal cell carcinoma lesion that is considered to be inoperable or to have medical contraindications to surgery * Recent (i.e., within the past 28 days prior to randomization) or current participation in another experimental drug study * Known or suspected alcohol abuse * One of the following known rare hereditary conditions: galactose intolerance, primary hypolactasia or glucose-galactose malabsorption
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment) | Baseline; Week 73 | The total number of clinically evident basal cell carcinomas = the total number of target and/or non-target lesions present in individual participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73 | Baseline; Week 73 | The three target basal cell carcinoma lesions = the three largest visible lesions, at least 5 mm in the longest diameter, in individual participants. |
| Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73 | Baseline; Week 73 | — |
| Percentage of Participants With New Basal Cell Carcinomas at Week 73 | Baseline; Week 73 | — |
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate) | Baseline; Week 85 | — |
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate) | Baseline; Week 97 | — |
| Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Baseline to Week 73 | The percentage of participants who discontinued study treatment (due either to adverse event, refusal of treatment, or withdrawal of consent) was summarized by treatment group. |
| Percentage of Participants Experiencing Any Adverse Event | Up to 125 weeks | — |
| Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73 | Baseline; Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their symptoms, and their answers were combined into a composite Symptom Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). |
| Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73 | Baseline; Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their emotional state, and their answers were combined into a composite Emotion Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). |
| Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73 | Baseline; Week 73 | The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their ability to function, and answers were combined into a composite Function Domain Score. Scores range from 0 (never bothered) to 100 (always bothered). |
| Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate) | Baseline; Week 125 | — |
Countries
Austria, Canada, France, Germany, Italy, Mexico, Netherlands, Russia, Spain, United States
Participant flow
Pre-assignment details
229 participants were enrolled in 10 countries.
Participants by arm
| Arm | Count |
|---|---|
| Vismodegib Intermittent Schedule Vismodegib intermittent schedule of 12 weeks vismodegib followed by 8 weeks placebo, repeated 3 times with a final course of vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up | 116 |
| Vismodegib Induction Followed by Intermittent Schedule Vismodegib beginning with 24 weeks induction followed by intermittent schedule 8 weeks placebo, 8 weeks vismodegib (total 72 weeks), followed by 52 weeks treatment-free follow up | 113 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative/Other | 1 | 3 |
| Overall Study | Adverse Event | 10 | 16 |
| Overall Study | Death | 2 | 2 |
| Overall Study | Disease progression | 3 | 2 |
| Overall Study | Investigators Decision | 2 | 3 |
| Overall Study | Lost to Follow-up | 3 | 6 |
| Overall Study | Missing | 1 | 0 |
| Overall Study | Refused Treatment | 5 | 1 |
| Overall Study | Sponsor Termination Treatment | 1 | 0 |
| Overall Study | Withdrew Consent | 31 | 30 |
Baseline characteristics
| Characteristic | Vismodegib Intermittent Schedule | Vismodegib Induction Followed by Intermittent Schedule | Total |
|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 13.94 | 59.9 years STANDARD_DEVIATION 15.35 | 60.5 years STANDARD_DEVIATION 14.63 |
| Sex: Female, Male Female | 35 Participants | 25 Participants | 60 Participants |
| Sex: Female, Male Male | 81 Participants | 88 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 114 | 108 / 113 |
| serious Total, serious adverse events | 24 / 114 | 23 / 113 |
Outcome results
Primary
Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment)
The total number of clinically evident basal cell carcinomas = the total number of target and/or non-target lesions present in individual participants.
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat analysis population (defined as all randomized participants) with available data were included in the analysis. The last observation carried forward method was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment) | 62.9 percent change | Standard Deviation 52.01 |
| Vismodegib Induction Followed by Intermittent Schedule | Mean Percent Change From Baseline in the Number of Clinically Evident Basal Cell Carcinomas at Week 73 (After 72 Weeks of Treatment) | 54.9 percent change | Standard Deviation 54.85 |
Comparison: The mean difference in the mean relative reduction between treatment arms, along with the corresponding 95% confidence interval, was estimated by fitting an ANCOVA model with treatment as main effect and the following covariates: number of basal cell carcinomas at baseline, geographical region, immunosuppression status, confirmed basal cell carcinoma nevus syndrome.95% CI: [-22.2, 5.7]
Secondary
Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73
The three target basal cell carcinoma lesions = the three largest visible lesions, at least 5 mm in the longest diameter, in individual participants.
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73 | 82.9 percent change | Standard Deviation 27.01 |
| Vismodegib Induction Followed by Intermittent Schedule | Mean Percent Change From Baseline in Total Size of Three Target Basal Cell Carcinoma Lesions in Individual Participants at Week 73 | 68.0 percent change | Standard Deviation 53.02 |
Secondary
Percentage of Participants Experiencing Any Adverse Event
Time frame: Up to 125 weeks
Population: Safety Analysis Population: participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vismodegib Intermittent Schedule | Percentage of Participants Experiencing Any Adverse Event | 99.1 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants Experiencing Any Adverse Event | 97.3 percentage of participants |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues
The percentage of participants who discontinued study treatment (due either to adverse event, refusal of treatment, or withdrawal of consent) was summarized by treatment group.
Time frame: Baseline to Week 73
Population: Intent-to-Treat Analysis Population, defined as all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Overall | 37.1 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Adverse Events | 20.7 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Refused Treatment | 6.0 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Withdrew Consent | 10.3 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Withdrew Consent | 11.5 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Overall | 41.6 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Refused Treatment | 2.7 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants Who Discontinued Study Treatment Due to Tolerability Issues | Adverse Events | 27.4 percentage of participants |
Secondary
Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73
Time frame: Baseline; Week 73
Population: Intent-to-Treat Analysis Population, defined as all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vismodegib Intermittent Schedule | Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73 | 65.5 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With at Least 50% Reduction in the Number of Basal Cell Carcinomas at Week 73 | 50.4 percentage of participants |
Secondary
Percentage of Participants With New Basal Cell Carcinomas at Week 73
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 1 new lesion | 10.6 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 3 new lesions | 5.3 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 2 new lesions | 5.3 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | >3 new lesions | 2.1 percentage of participants |
| Vismodegib Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | No new lesions | 76.6 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | >3 new lesions | 5.8 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | No new lesions | 74.4 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 1 new lesion | 11.6 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 2 new lesions | 5.8 percentage of participants |
| Vismodegib Induction Followed by Intermittent Schedule | Percentage of Participants With New Basal Cell Carcinomas at Week 73 | 3 new lesions | 2.3 percentage of participants |
Secondary
Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73
The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their emotional state, and their answers were combined into a composite Emotion Domain Score. Scores range from 0 (never bothered) to 100 (always bothered).
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73 | -27.4 percent change | Standard Deviation 27.71 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Emotion Domain Score at Week 73 | -28.9 percent change | Standard Deviation 28.16 |
Secondary
Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73
The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their ability to function, and answers were combined into a composite Function Domain Score. Scores range from 0 (never bothered) to 100 (always bothered).
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73 | -9.5 percent change | Standard Deviation 20.59 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Function Domain Score at Week 73 | -10.3 percent change | Standard Deviation 26.03 |
Secondary
Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73
The Skindex-16 is a patient-reported outcome health questionnaire. Participants were asked about their symptoms, and their answers were combined into a composite Symptom Domain Score. Scores range from 0 (never bothered) to 100 (always bothered).
Time frame: Baseline; Week 73
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73 | -14.9 percent change | Standard Deviation 25.75 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change From Baseline in the Skindex-16 Symptom Domain Score at Week 73 | -12.6 percent change | Standard Deviation 23.98 |
Secondary
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate)
Time frame: Baseline; Week 125
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate) | 41.2 percent change | Standard Deviation 45.23 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 125 (52 Weeks Following End of Treatment) (Recurrence Rate) | 44.0 percent change | Standard Deviation 42.87 |
Secondary
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate)
Time frame: Baseline; Week 85
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate) | 35.7 percent change | Standard Deviation 50.25 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 85 (12 Weeks Following End of Treatment) (Recurrence Rate) | 38.5 percent change | Standard Deviation 55.22 |
Secondary
Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate)
Time frame: Baseline; Week 97
Population: Participants in the Intent-to-Treat Analysis Population (defined as all randomized participants) with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vismodegib Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate) | 36.0 percent change | Standard Deviation 49.48 |
| Vismodegib Induction Followed by Intermittent Schedule | Percent Change in Total Number of Basal Cell Carcinomas Relative to Baseline at Week 97 (24 Weeks Following End of Treatment) (Recurrence Rate) | 42.1 percent change | Standard Deviation 57.83 |