Description:
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.
Title
- Brief Title: Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer
- Official Title: A Phase 2 Open-Label, Single-Arm Trial of the Efficacy of Topical Remetinostat on Basal Cell Carcinoma in Patients
Clinical Trial IDs
- ORG STUDY ID:
IRB-40947
- SECONDARY ID:
NCI-2017-00981
- SECONDARY ID:
SKIN0037
- NCT ID:
NCT03180528
Conditions
- Skin Basal Cell Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Remetinostat | suberohydroxamic acid phenyl ester (SHAPE); SHAPE Gel; SHP 141; and 4 [[8 (hydroxyamino) 1,8 dioxooctyl]oxy] benzoic acid methyl ester | Treatment (remetinostat) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (remetinostat) | Experimental | Patients receive topical remetinostat 1% gel applied TID directly to the lesion, for 6 weeks in the absence of disease progression or unacceptable toxicity. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate |
Time Frame: | At 6 weeks |
Safety Issue: | |
Description: | 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 Outcome Measures
Measure: | Number of Participants With a Decrease in Expression of the Hedgehog Biomarker Gene GLI1 |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Adverse Events Contributing to Treatment Discontinuation or Interruption |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | Adverse events (AEs) contributing to treatment discontinuation or interruption are reported as the number of such events, a number without dispersion. |
Measure: | Participants Who Discontinued Treatment or Had Treatment Interruption |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Kavita Sarin |
Last Updated
June 8, 2021