Skin Basal Cell Carcinoma
Conditions
Brief summary
This phase 2 trial studies how well remetinostat works in treating patients with skin basal cell cancer. Remetinostat may slow the growth of basal cell cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. Overall response rate of basal cell carcinoma (BCC) in subjects at 6 weeks. SECONDARY OBJECTIVES: I. Suppression of GLI1 (glioma-associated oncogene) expression in treated BCCs as compared with baseline. II. Safety assessment of Remetinostat after 6 weeks of topical treatment. OUTLINE: Tumors receive Remetinostat topically three times per day (TID) for 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for at least 4 weeks.
Interventions
DRUGRemetinostat
Applied topically under bandage occlusion
Sponsors
Medivir
National Institutes of Health (NIH)
American Skin Association
Kavita Sarin
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
* Must have at least one BCC lesion \> 1 cm (BCC \> 5 mm) in non-cosmetically sensitive site(s) * Must be willing to apply the topical remetinostat 3 times daily for 6 weeks * For women of child bearing potential, a negative urine pregnancy test * Women of child bearing potential are expected to use an effective method of birth control while participating in the study and for 1 month after applying the last dose * For male subjects with female partners of childbearing potential, agreement to use adequate contraception while participating in the study and for 1 month after applying the last dose * Has signed and dated the current Institutional Review Board (IRB) approved informed consent document
Exclusion criteria
* Taking any medication known to interact with histone deacetylase (HDAC) inhibitors, such as valproate or anticoagulants * Taking any medication known to affect hedgehog (HH) signaling pathway such as itraconazole * Within the past 6 months, has used topical or systemic therapies that might interfere with the evaluation of the study medication during the study; specifically, these include the topical use to the study tumors of: * Glucocorticoids * Retinoids either systemically or topically (eg, etretinate, isotretinoin, tazarotene, tretinoin, adapalene) * Alpha hydroxy acids (eg, glycolic acid, lactic acid) to \> 5% of the skin * 5 fluorouracil or imiquimod and/or * Itraconazole * Has received treatment with systemic chemotherapy or agents known to be inhibitors of HH signaling, within 60 days to starting study medication * Currently receiving systemic medications that could affect BCC tumors (eg, oral retinoids) or might interact with remetinostat * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, recurrent seizure history or psychiatric illness/social situations that would limit compliance with study requirements * Moderate to severe immunosuppression due to disease or medication * Known or previous hypersensitivity to histone deacetylase inhibitor (HDACi) * History of congestive heart failure; cardiac arrhythmias; or other findings of ventricular dysfunction * History of current evidence of malabsorption or liver disease * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | At 6 weeks | Overall response is defined as achieving either a complete response (CR) or a partial response (PR). Response is based on the Response Evaluation Criteria in Solid Tumors (RECIST), as follows. * CR = tumor lesion becomes undetectable * PR = ≥30% decrease in total tumor diameter * Overall response (OR) = CR+PR * Stable Disease (SD) = decrease in total tumor diameter is \>0% and \<30% * Progressive Disease (PD) = increase in total tumor diameter Exact binomial 90% confidence intervals (90%) will be computed for OR. The data are reported accord to the per protocol analysis, ie, including lesions for subjects who were \<70% compliant with drug treatment. For subjects who were compliant but dropped out, data from their last study visit will be used if they contribute a biopsy. The analysis population will include the participants who have provided pre-treatment and post-treatment biopsies. The outcome is reported as the percent of tumor lesions that achieve OR, with 90% CI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Decrease in Expression of the Hedgehog Biomarker Gene GLI1 | 6 weeks | The effect of topical remetinostat gel 1% on decreasing expression of Hedgehog biomarker gene GLI1 was determined using the RNeasy Fibrous Tissue Mini Kit (Qiagen, Valencia, CA), a polymerase chain reaction (PCR) test kit. The levels observed at baseline and after 6 weeks treatment were obtained. The outcome is reported as the number of subjects for whom a decrease in expression of the Hedgehog biomarker gene GLI1 was observed, a number without dispersion. |
| Adverse Events Contributing to Treatment Discontinuation or Interruption | 6 weeks | Adverse events (AEs) contributing to treatment discontinuation or interruption are reported as the number of such events, a number without dispersion. |
| Participants Who Discontinued Treatment or Had Treatment Interruption | 6 weeks | The number of participants who discontinued treatment or experienced treatment interruption within the first 6 weeks of treatment are reported as the number of such participants, a number without dispersion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Remetinostat) Patients receive topical remetinostat 1% gel applied TID directly to the lesion, for 6 weeks in the absence of disease progression or unacceptable toxicity.
Remetinostat: Applied topically under bandage occlusion | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Eligible and enrolled, but withdrawn due to abnormal baseline laboratory values. | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Remetinostat) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 59.26 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 3 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Overall Response Rate
Overall response is defined as achieving either a complete response (CR) or a partial response (PR). Response is based on the Response Evaluation Criteria in Solid Tumors (RECIST), as follows. * CR = tumor lesion becomes undetectable * PR = ≥30% decrease in total tumor diameter * Overall response (OR) = CR+PR * Stable Disease (SD) = decrease in total tumor diameter is \>0% and \<30% * Progressive Disease (PD) = increase in total tumor diameter Exact binomial 90% confidence intervals (90%) will be computed for OR. The data are reported accord to the per protocol analysis, ie, including lesions for subjects who were \<70% compliant with drug treatment. For subjects who were compliant but dropped out, data from their last study visit will be used if they contribute a biopsy. The analysis population will include the participants who have provided pre-treatment and post-treatment biopsies. The outcome is reported as the percent of tumor lesions that achieve OR, with 90% CI.
Time frame: At 6 weeks
Population: Analysis is on a per-lesion basis, and not a per-participant basis. Per protocol, analysis does not include lesions from participants \<70% compliant with treatment regimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Remetinostat) | Overall Response Rate | 69.7 percentage of tumor lesions |
Secondary
Adverse Events Contributing to Treatment Discontinuation or Interruption
Adverse events (AEs) contributing to treatment discontinuation or interruption are reported as the number of such events, a number without dispersion.
Time frame: 6 weeks
Population: The outcome is reported as a number of adverse events (AEs), not as a number of participants. For some participants, multiple AEs contributing to treatment decisions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Remetinostat) | Adverse Events Contributing to Treatment Discontinuation or Interruption | AEs contributing to treatment interruption | 9 adverse events |
| Treatment (Remetinostat) | Adverse Events Contributing to Treatment Discontinuation or Interruption | AEs contributing to treatment discontinuation | 3 adverse events |
Secondary
Number of Participants With a Decrease in Expression of the Hedgehog Biomarker Gene GLI1
The effect of topical remetinostat gel 1% on decreasing expression of Hedgehog biomarker gene GLI1 was determined using the RNeasy Fibrous Tissue Mini Kit (Qiagen, Valencia, CA), a polymerase chain reaction (PCR) test kit. The levels observed at baseline and after 6 weeks treatment were obtained. The outcome is reported as the number of subjects for whom a decrease in expression of the Hedgehog biomarker gene GLI1 was observed, a number without dispersion.
Time frame: 6 weeks
Population: Results are reported for those participants for whom baseline and 6-week analysis data were available. The COVID-19 epidemic adversely affected the ability of the laboratory to process and return results.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Remetinostat) | Number of Participants With a Decrease in Expression of the Hedgehog Biomarker Gene GLI1 | 5 Participants |
Secondary
Participants Who Discontinued Treatment or Had Treatment Interruption
The number of participants who discontinued treatment or experienced treatment interruption within the first 6 weeks of treatment are reported as the number of such participants, a number without dispersion.
Time frame: 6 weeks
Population: For some participants, multiple AEs contributing to the treatment decision.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Remetinostat) | Participants Who Discontinued Treatment or Had Treatment Interruption | Participants who experienced treatment interruption | 5 Participants |
| Treatment (Remetinostat) | Participants Who Discontinued Treatment or Had Treatment Interruption | Participants who discontinued treatment | 3 Participants |