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Open Label, Dose Escalation Study for the Safety and Efficacy of STP705 in Adult Patients With isSCC

NCT04293679

Description:

This is an open label, dose escalation study to evaluate the safety and efficacy of intralesional injection of STP705 in adult patients with Cutaneous Squamous Cell Carcinoma in situ (isSCC, Bowen's disease). The purpose of this trial is to evaluate the safety, tolerability and efficacy of various doses of STP705 administered as Intralesional injection in subjects with isSCC. Goals: - To determine the safe and effective recommended dose of STP705 for the treatment of isSCC. - Analysis of biomarkers common to isSCC formation pathway including TGF-β1 and COX-2.

Related Conditions:
  • Skin Squamous Cell Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Open Label, Dose Escalation Study for the Safety and Efficacy of STP705 in Adult Patients With isSCC
  • Official Title: An Open Label, Dose Escalation Study to Evaluate the Safety and Efficacy of Intralesional Injection of STP705 in Adult Patients With Cutaneous Squamous Cell Carcinoma in Situ (isSCC)

Clinical Trial IDs

  • ORG STUDY ID: SRN-705-004
  • NCT ID: NCT04293679

Conditions

  • Bowen's Disease
  • Cutaneous Squamous Cell Carcinoma in Situ

Interventions

DrugSynonymsArms
STP705Cohort A: STP705 10 μg dose

Purpose

This is an open label, dose escalation study to evaluate the safety and efficacy of intralesional injection of STP705 in adult patients with Cutaneous Squamous Cell Carcinoma in situ (isSCC, Bowen's disease). The purpose of this trial is to evaluate the safety, tolerability and efficacy of various doses of STP705 administered as Intralesional injection in subjects with isSCC. Goals: - To determine the safe and effective recommended dose of STP705 for the treatment of isSCC. - Analysis of biomarkers common to isSCC formation pathway including TGF-β1 and COX-2.

Detailed Description

      This open label, dose escalation study is designed to evaluate the safety and efficacy of
      various doses of STP705 administered as an intralesional injection in subjects with cutaneous
      in situ squamous cell carcinoma (isSCC).

      The primary objective of this study is to evaluate the safety, tolerability, and efficacy of
      various doses of STP705 administered as an Intralesional injection in subjects with cutaneous
      squamous cell carcinoma in situ skin cancer (isSCC). This study seeks to establish a safe and
      effective recommended dose of STP705 for the treatment of isSCC. Expression of biomarkers
      common to the isSCC formation pathway, including TGF-β1 and COX-2, will be evaluated.

      The primary endpoint will be the proportion of participants with histological clearance of
      treated isSCC lesion at the End of Treatment (EOT). Histological clearance (HC) will be
      defined as the absence of detectable evidence of isSCC tumor cell nests as determined by
      central pathology review.

      Secondary endpoints will include i) time to histological clearance of treated isSCC lesion
      over the 6 week treatment period, ii) proportion of participants with complete clinical
      clearance of treated isSCC lesion based on investigator assessment at the End of Treatment
      (EOT), iii) time to complete clinical clearance of treated isSCC lesion based on investigator
      assessment over the 6 week treatment period, and iv) the change in size of the treated isSCC
      lesion over the 6 week treatment period.

      Safety and tolerability will be assessed by the number of incidence of adverse events (AEs)
      and serious adverse events (SAEs); the incidence of AEs and SAEs leading to discontinuation
      of trial medication; the incidence and severity of Local Skin Response (LSR);
      hypopigmentation and hyperpigmentation following treatment; and the tolerability of repeated
      Intralesional administration of STP705 as assessed by investigator-evaluation of injection
      site reactions for all patients and within each cohort.

      In addition, safety measures will include clinically relevant changes or new abnormal
      findings in laboratory values, vital signs, electrocardiograms (ECGs), and physical
      examination variables.

      25 adult patients are planned to be enrolled in the study. They will be divided equally among
      5 cohorts (10, 20, 30, 60 and 120 μg dose levels) of 5 subjects each. Enrollment of the first
      two subjects in each dosing cohort will be staggered by at least 48 hours. Participants in
      the first cohort will attend the study center once weekly for an injection of STP705 into the
      isSCC lesion. The participants will receive injections of STP705 once a week for up to 6
      weeks. The clinician will evaluate the tumor for clinical changes and reduction in size at
      each treatment visit for up to 6 weeks. If during the 6 weeks of treatment there is complete
      clinical clearance of the tumor, the treatments will end. At the End of Treatment visit, the
      residual tumor, or former tumor location will be excised for analysis. In the absence of dose
      limiting toxicities (DLT), the subsequent cohorts will receive increasing doses of STP705,
      following the same schedule of administration as the first cohort.

      If any of the SAEs or dose limiting toxicities outlined above has occurred, the Data Safety
      Monitoring Board (DSMB) will conduct independent review of the data and will make a final
      decision for dose escalation to the next cohort.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A: STP705 10 μg doseExperimentalCohort A: STP705 10 μg dose, intradermal injection, given once a week for up to 6 weeks
  • STP705
Cohort B: STP705 20 μg doseExperimentalCohort B: STP705 20 μg dose, intradermal injection, given once a week for up to 6 weeks
  • STP705
Cohort C: STP705 30 μg doseExperimentalCohort C: STP705 30 μg dose, intradermal injection, given once a week for up to 6 weeks
  • STP705
Cohort D: STP705 60 μg doseExperimentalCohort D: STP705 60 μg dose, intradermal injection, given once a week for up to 6 weeks
  • STP705
Cohort E: STP705 120 μg doseExperimentalCohort E: STP705 120 μg dose, intradermal injection, given once a week for up to 6 weeks
  • STP705

Eligibility Criteria

        Inclusion Criteria:

          -  1. Male or female adult ≥ 18 years of age.

          -  2. Primary, histologically confirmed trunk or extremity
             (non-peri-orbital/-anogenital/-facial/-scalp) isSCC lesion suitable for excision with
             a minimum diameter of 0.5cm and with a maximum diameter of 2.0cm.

          -  3. Histological diagnosis made no more than 6 months prior to the screening visit.

          -  4. Histological biopsy removed ≤25% of the original area of the target lesion.

          -  5. No other dermatological disease in the isSCC target site or surrounding area, which
             in the opinion of the investigator, could interfere with the study.

          -  6. Willing to refrain from using non-approved lotions or creams on the target site and
             surrounding area during the treatment period.

          -  7. Willing to refrain from exposure to excessive direct sunlight or ultraviolet light
             and to avoid the use of tanning parlors for the duration of the study.

          -  8. Laboratory values for the tests (listed in the Study Schedule) within the reference
             ranges as defined by the central laboratory, or "out of range" test results that is
             clinically acceptable to the investigator. Acceptable "out of range" values are
             generally those within 2 standard deviations of the mean or explainable due to
             concurrent medications or disease processes.

          -  9. Ability to follow study instructions and likely to complete all study requirements.

          -  10. Written informed consent obtained, including consent for tissue to be examined and
             stored by the Central Histology Lab.

          -  11. Written consent to allow photographs of the target isSCC lesion to be used as part
             of the study data and documentation.

          -  12. For females of childbearing potential, a negative pregnancy test at screening and
             using an acceptable form of birth control (oral / implant/ injectable/ transdermal
             contraceptives, intrauterine device, condom, diaphragm, abstinence, or a monogamous
             relationship with a partner who has had a vasectomy).

        Exclusion Criteria:

          -  1. Pregnant or lactating.

          -  2. Presence of known or suspected systemic cancer.

          -  3. Histological evidence of nBCC, sBCC, invasive SCC, or any other non-isSCC tumor in
             the biopsy specimen.

          -  4. Histological evidence of severe squamous metaplasia, infiltrative, desomoplastic or
             micronodular growth patterns in the biopsy specimen.

          -  5. History of recurrence of the target isSCC lesion.

          -  6. Prior exposure to STP705.

          -  7. Evidence of dermatological disease or confounding skin condition in the treatment
             area, e.g., BCC, actinic keratosis, rosacea, psoriasis, atopic dermatitis, eczema,
             xeroderma pigmentosa.

          -  8. Concurrent disease or treatment that suppresses the immune system;

          -  9. Patients with baseline QTC > 480 msec using Frederica's formula

          -  10. Chronic medical condition that in the judgment of the investigator(s) would
             interfere with the performance of the study or would place the patient at undue risk.

          -  11. Known sensitivity to any of the ingredients in the study medication.

          -  12. Use of a tanning beds or other excessive or prolonged exposure to ultraviolet
             light or direct sunlight during the study.

          -  13. Treatment with systemic chemotherapeutic agents within the 6 months prior to the
             screening visit.

          -  14. Use of systemic retinoids within the 6 months prior to the screening period.

          -  15. Treatment with systemic immunomodulators or immunosuppressants within the 6 months
             prior to the screening period.

          -  16. Use of topical immunomodulators within 2cm of the target isSCC lesion within the 4
             weeks prior to the screening period.

          -  17. Treatment with the following topical agents within 2cm of the target isSCC lesion
             within the 4 weeks prior to the screening visit: amino-levulanic acid, 5-fluorouracil,
             corticosteroids, retinoids, diclofenac, ingenol mebutate, or imiquimod.

          -  18. Treatment with liquid nitrogen, surgical excision (excluding diagnostic incisional
             biopsy) or curettage within 2cm of the target isSCC lesion during the 4 weeks prior to
             the screening visit.

          -  19. Elective surgery within 4 weeks prior to the screening visit, during the study, or
             4 weeks after the study period.

          -  20. Evidence of current chronic alcohol or drug abuse.

          -  21. Current enrollment in an investigational drug or device study or participation in
             such a study within 4 weeks of the screening visit.

          -  22. In the investigator's opinion, evidence of unwillingness, or inability to follow
             the restrictions and requirements of the protocol and complete the study.

          -  23. Taking any investigational product within 1 month of first dose of STP705.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of participants with histological clearance of treated isSCC lesion at the End of Treatment (EOT).
Time Frame:6 weeks
Safety Issue:
Description:Proportion of participants with histological clearance of treated isSCC lesion at the End of Treatment (EOT). Histological clearance (HC) will be defined as the absence of detectable evidence of isSCC tumor cell nests as determined by central pathology review.

Secondary Outcome Measures

Measure:Time to histological clearance of treated isSCC lesion over the 6 week treatment period.
Time Frame:over the 6 week treatment period
Safety Issue:
Description:
Measure:Proportion of participants with complete clinical clearance of treated isSCC lesion based on investigator assessment at the End of Treatment (EOT).
Time Frame:6 weeks
Safety Issue:
Description:
Measure:Time to complete clinical clearance of treated isSCC lesion based on investigator assessment over the 6 week treatment period.
Time Frame:over the 6 week treatment period
Safety Issue:
Description:
Measure:Change in size of the treated isSCC lesion over the 6 week treatment period.
Time Frame:over the 6 week treatment period
Safety Issue:
Description:Change in size of the treated isSCC lesion over the 6 week treatment period. A base line assessment of lesion size will be made by investigator at T1 (first visit, Day 0). The change in size will be assessed every week until the surgical excision of isSCC at the End of Treatment visit (EOT, Day 42) .

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sirnaomics

Trial Keywords

  • isSCC
  • Cutaneous Squamous Cell Carcinoma
  • STP705
  • Cutaneous Squamous Cell Carcinoma in situ
  • Bowen's disease
  • Bowen's

Last Updated

February 28, 2020