Basal Cell Carcinoma
Conditions
Brief summary
This was a 3-cohort, open-label study of vismodegib (GDC-0449) in new (non-recurrent) operable basal cell carcinoma of the nodular subtype.
Detailed description
For Cohort 1, the response to treatment was determined at the end of the 12 weeks of treatment. For Cohort 2, the response to treatment was determined after 12 weeks of treatment and 24 weeks of observation. For Cohort 3, the response to treatment was determined after intermittent dosing over a 20-week period, consisting of an initial 8-week treatment period, followed by a 4-week drug holiday period, followed by a second 8-week treatment period.
Interventions
DRUGVismodegib
Vismodegib was supplied in gelatin capsules.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed new (not recurrent or previously treated) nodular basal cell carcinoma (BCC) at 1 of the listed anatomical sites, which must be biopsy confirmed at the study site. * Willingness to consent to biopsy of the lesion. * Willingness to delay excision of the target tumor site until the time mandated in the protocol, unless evidence of disease progression or lack of drug tolerability. * Adequate hematopoietic capacity. * Adequate hepatic function. * For women of childbearing potential, agreement to use 2 acceptable forms of birth control (including one barrier method) during the study and for 7 months after discontinuation of study drug. * For men with female partners of childbearing potential, agreement to use a male condom (with spermicide) and to advise their female partners to use an additional acceptable method of birth control during the study and for 2 months after discontinuation of study drug. * Agreement not to donate blood/blood products during the study and for 7 months after discontinuing study drug. * Agreement not to donate sperm or semen during treatment and for 2 months after the last dose of vismodegib.
Exclusion criteria
* Prior treatment with vismodegib or any Hedgehog pathway inhibitor. * Inability or unwillingness to swallow capsules. * Pregnancy or lactation. * BCC with any clinical and histological pattern other than nodular BCC. * Patients with known Gorlin's syndrome (basal cell nevus syndrome) or clinical suspicion of Gorlin's syndrome. * Recent (ie, within the past 28 days), current, or planned participation in another experimental drug study. * Use of any excluded medication or therapy within 21 days of study entry. * History of other malignancies within 3 years of the first day of treatment (Day 1), except for tumors with a negligible risk of metastasis, such as other non-melanoma skin cancer (BCC, squamous cell cancer), ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix. * Uncontrolled medical illness. * History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications. * Any medical or psychological illness or condition preventing adequate consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Histologic Clearance | Baseline to Week 12 (Cohort 1), Baseline to Week 36 (Cohort 2), Baseline to Week 20 (Cohort 3) | Complete histologic clearance was defined as the absence of histological evidence of basal cell carcinoma at the target tumor site. Histological examination was performed by an independent pathologist on specimens collected within 2 weeks of the end of treatment period, ie, at 12 weeks after Baseline in Cohort 1, at 36 weeks after Baseline in Cohort 2, and at 20 weeks after Baseline in Cohort 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Complete Clinical Clearance | Baseline to the end of the study (up to 12 weeks for Cohort 1; up to 36 weeks for Cohort 2, up to 20 weeks for Cohort 3) | Time to complete clinical clearance was defined as the time from the first treatment with vismodegib until complete clinical clearance as determined by the investigator. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Vismodegib 150 mg Participants received vismodegib 150 mg orally daily for 12 weeks. | 24 |
| Cohort 2: Vismodegib 150 mg Participants received vismodegib 150 mg orally daily for 12 weeks. | 25 |
| Cohort 3: Vismodegib 150 mg Participants received vismodegib 150 mg orally daily for 8 weeks, followed by 4 weeks with no treatment, followed by a second 8-week vismodegib treatment period. | 25 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 4 | 0 |
| Overall Study | Physician Decision | 3 | 0 | 0 |
| Overall Study | Subject Decision | 3 | 3 | 5 |
| Overall Study | Target Lesion Progression | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Vismodegib 150 mg | Cohort 2: Vismodegib 150 mg | Cohort 3: Vismodegib 150 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 11.2 | 65.2 years STANDARD_DEVIATION 13.3 | 65.1 years STANDARD_DEVIATION 11.8 | 63.6 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 19 Participants | 22 Participants | 17 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 25 / 25 | 24 / 25 |
| serious Total, serious adverse events | 0 / 24 | 3 / 25 | 3 / 25 |
Outcome results
Primary
Percentage of Participants With Complete Histologic Clearance
Complete histologic clearance was defined as the absence of histological evidence of basal cell carcinoma at the target tumor site. Histological examination was performed by an independent pathologist on specimens collected within 2 weeks of the end of treatment period, ie, at 12 weeks after Baseline in Cohort 1, at 36 weeks after Baseline in Cohort 2, and at 20 weeks after Baseline in Cohort 3.
Time frame: Baseline to Week 12 (Cohort 1), Baseline to Week 36 (Cohort 2), Baseline to Week 20 (Cohort 3)
Population: Efficacy evaluable population: All participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Vismodegib 150 mg | Percentage of Participants With Complete Histologic Clearance | 42.0 Percentage of participants |
| Cohort 2: Vismodegib 150 mg | Percentage of Participants With Complete Histologic Clearance | 16.0 Percentage of participants |
| Cohort 3: Vismodegib 150 mg | Percentage of Participants With Complete Histologic Clearance | 44.0 Percentage of participants |
Comparison: The null hypothesis was that percentage of participants with complete histologic clearance was 50% or less.p-value: 0.84631-sided exact binomial test
Comparison: The null hypothesis was that percentage of participants with complete histologic clearance was 30% or less.p-value: 0.96681-sided exact binomial test
Comparison: The null hypothesis was that percentage of participants with complete histologic clearance was 50% or less.p-value: 0.78781-sided exact binomial test
Secondary
Time to Complete Clinical Clearance
Time to complete clinical clearance was defined as the time from the first treatment with vismodegib until complete clinical clearance as determined by the investigator.
Time frame: Baseline to the end of the study (up to 12 weeks for Cohort 1; up to 36 weeks for Cohort 2, up to 20 weeks for Cohort 3)
Population: Efficacy evaluable population: All participants who were treated with at least 1 dose of study drug. Only participants who achieved complete clinical clearance were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Vismodegib 150 mg | Time to Complete Clinical Clearance | 59.5 Days |
| Cohort 2: Vismodegib 150 mg | Time to Complete Clinical Clearance | 84.0 Days |
| Cohort 3: Vismodegib 150 mg | Time to Complete Clinical Clearance | 60.0 Days |