Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Skin Basal Cell Carcinoma
• Intervention / Treatment: Drug: Remetinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Remetinostat; Applied topically under bandage occlusion; 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

Collaborators and Investigators

• Sponsor: Kavita Sarin
• Collaborators: National Institutes of Health (NIH); Medivir; American Skin Association
• Investigators: Principal Investigator: Kavita Sarin, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2018
• Primary Completion (Actual): July 7, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Anti-Infective Agents; Antifungal Agents; Benzoic Acid
• Other Study ID Numbers: IRB-40947; NCI-2017-00981 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SKIN0037 (Other Identifier: Stanford)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No