Clinical Trials /

Topical Remetinostat in Treating Patient With Cutaneous Basal Cell Cancer

NCT03180528

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.

Related Conditions:
  • Basal Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Remetinostatsuberohydroxamic acid phenyl ester (SHAPE); SHAPE Gel; SHP 141; and 4 [[8 (hydroxyamino) 1,8 dioxooctyl]oxy] benzoic acid methyl esterTreatment (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

NameTypeDescriptionInterventions
Treatment (remetinostat)ExperimentalPatients receive topical remetinostat 1% gel applied TID directly to the lesion, for 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Remetinostat

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