Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer

Study Overview
=================
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.

Official Title
-----------------
A Phase 2 Open-Label, Single-Arm Trial of the Efficacy of Topical Remetinostat on Basal Cell Carcinoma in Patients

Conditions
-----------------
Skin Basal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Remetinostat


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (remetinostat)<br>Patients receive topical remetinostat 1% gel applied TID directly to the lesion, for 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Remetinostat<br>* Applied topically under bandage occlusion<br>* Other names: suberohydroxamic acid phenyl ester (SHAPE); SHAPE Gel; SHP 141; and 4 [[8 (hydroxyamino) 1,8 dioxooctyl]oxy] benzoic acid methyl ester;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 
| 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. | 6 weeks | 
| 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. | 6 weeks |