Basal Cell Carcinoma of the Skin, Recurrent Skin Cancer
Conditions
Brief summary
This pilot clinical trial studies arsenic trioxide in treating patients with basal cell carcinoma. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stop them from dividing
Detailed description
PRIMARY OBJECTIVES: I. To determine whether administration of arsenic trioxide (ATO) to patients with basal cell carcinoma is associated with a reduction in Gli messenger ribonucleic acid (mRNA) and protein levels in tumor biopsy samples, when compared to baseline levels. SECONDARY OBJECTIVES: I. To determine whether there is evidence of tumor size reduction of ATO against basal cell carcinoma in humans. OUTLINE: Patients receive arsenic trioxide intravenously (IV) over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGarsenic trioxide
Given IV
Sponsors
The V Foundation for Cancer Research
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Basal cell carcinoma (BCC) * Ineligible for curative locoregional treatment and have either progressed on, did not tolerate, unwilling to try or ineligible for investigational smoothened antagonist such as vismodegib (GDC 0449), XL 139 (BMS 833923), IPI- 926, LDE225 and PF-04449913 * Life expectancy estimate \> 3 months * Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal * Creatinine within normal institutional limits * Corrected QT interval (QTC) by 12 lead electrocardiogram (EKG) \< 450 msecs * Serum potassium within normal limits * Magnesium within normal limits * Calcium within normal limits * Ability to understand and the willingness to sign a written informed consent document * Evaluable tumor and be potentially eligible for pre and post ATO tumor biopsy * Receiving potassium wasting diuretics or amphotericin, while not excluded, must be noted to have theoretically increased arrhythmia risks with ATO
Exclusion criteria
* Concurrent use of other Investigational agents * Cardiac arrhythmias * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recurrent seizure history or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in Biomarker (GLI2 Protein) Levels | baseline to day 33 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With Stable Disease Post Treatment | After 3 cycles of treatment (approx. 61 days) | Number of patients with stable disease post treatment by RECIST criteria |
| Patients With Progressive Disease Post Treatment by RECIST Criteria | After 3 treatment cycles (approx. 61 days) | Patients with a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Incidence of Grade 3/4 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | Baseline to cycle 3 | — |
Countries
United States
Participant flow
Recruitment details
We will recruit from medical clinic and other physicians who treat metastatic BCC
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Arsenic Trioxide) arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Treatment (Arsenic Trioxide) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Percent Change in Biomarker (GLI2 Protein) Levels
Time frame: baseline to day 33
Population: We recruited patients with biopsy-confirmed metastatic basal cell carcinoma who were had progressed on SMO inhibitors such as vismodegib (GDC 0449), IPI- 926, LEQ506 and LDE225.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Arsenic Trioxide) | Percent Change in Biomarker (GLI2 Protein) Levels | 75 percentage decrease | Standard Deviation 11 |
Secondary
Incidence of Grade 3/4 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Time frame: Baseline to cycle 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Arsenic Trioxide) | Incidence of Grade 3/4 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | 2 number of occurrences |
Secondary
Patients With Progressive Disease Post Treatment by RECIST Criteria
Patients with a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: After 3 treatment cycles (approx. 61 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Arsenic Trioxide) | Patients With Progressive Disease Post Treatment by RECIST Criteria | 1 participants |
Secondary
Patients With Stable Disease Post Treatment
Number of patients with stable disease post treatment by RECIST criteria
Time frame: After 3 cycles of treatment (approx. 61 days)
Population: 4 patients completed 3 cycles of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Arsenic Trioxide) | Patients With Stable Disease Post Treatment | 3 participants |