Clinical Trials /

Intra-lesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma

NCT03316274

Description:

There is no clear treatment for patients with limited cutaneous Kaposi sarcoma (KS). Radiation and injection of vinblastine both have side effects that may not be acceptable. Nivolumab has been used to treat more extensive KS when given intravenously. This is, to the investigators' knowledge, the first trial to see if nivolumab can be used as treatment in the form of an injection into KS lesion.

Related Conditions:
  • Kaposi Sarcoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intra-lesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma
  • Official Title: Phase 1 Study to Evaluate the Safety, Feasibility and Immunologic Correlatives of Intra-lesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: CC17872
  • NCT ID: NCT03316274

Conditions

  • Kaposi Sarcoma
  • HIV/AIDS
  • Immunosuppression

Interventions

DrugSynonymsArms
Intra-lesional injection of nivolumabNivolumab

Purpose

There is no clear treatment for patients with limited cutaneous Kaposi sarcoma (KS). Radiation and injection of vinblastine both have side effects that may not be acceptable. Nivolumab has been used to treat more extensive KS when given intravenously. This is, to the investigators' knowledge, the first trial to see if nivolumab can be used as treatment in the form of an injection into KS lesion.

Detailed Description

      Infection with Kaposi sarcoma herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) causes
      Kaposi sarcoma (KS). These virally associated diseases occur more frequently in HIV-infected
      individuals, but can also be found in HIV-uninfected population. Evolution of
      immunosuppressive mechanisms presumably plays a permissive role in the development,
      progression and recurrence of these virus-associated cancers and pre-cancers. Currently,
      available treatment options for these lesions are imperfect.

      The goal of this study is to determine whether intra-lesional injections of nivolumab can
      enhance specific T cell responses in vitro and enhance activity against these
      virus-associated lesions. Chronic viral infections generate "exhausted" CD8+ T cells with a
      diminished capacity to produce cytokines and to lyse infected cells. The PD-1 (program
      death-1)/PD-L1 (program death ligand-1) pathway implicated in the balance between immune
      eradication and immune escape. This study will evaluate the safety, tolerability, and
      potential benefits of injecting nivolumab into KS in HIV-infected and HIV-uninfected
      individuals every 2 weeks for total of 4 doses. The investigators believe this mode of
      treatment is feasible and tolerable by avoiding the systemic autoimmune adverse events caused
      by systemic injection of nivolumab.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimental
  • Intra-lesional injection of nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed KS with active cutaneous disease and have less than 25
             lesions in total. They must not have symptomatic visceral KS or asymptomatic pulmonary
             KS.

        Cohort A (safety): treatment-experienced KS Cohort B: treatment-naïve KS

          -  For HIV-infected patients: CD4>350 cells/mm3 and HIV-1 viral load <75 copies/mL).

          -  Patients must have measurable cutaneous KS disease, defined as: 1 or more marker
             lesion that is bi-dimensionally measureable, and ≥0.5cm in shortest dimension. These
             lesions must not have received previous local radiation, surgical, or intra-lesional
             cytotoxic therapy that would prevent response assessment.

          -  Adequate organ function

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

        Exclusion Criteria:

          -  Prior systemic KS-directed treatments or investigational modalities ≤ 5 half-lives or
             4 weeks, whichever is shorter, prior to starting study drug or who have not recovered
             from side effects of such therapy to grade 1 or less.

          -  Hypersensitivity to nivolumab or any of its excipients

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Active systemic immunosuppressive therapy

          -  The use of prednisone or equivalent 10mg or greater a day that cannot be discontinued
             with more than 7 consecutive days of steroids within the prior 2 weeks.

          -  Prior organ allograft or allogeneic transplantation, if the transplanted tissue is
             still in place.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability as assessed by Common Terminology Criteria for Adverse Events version 4 (CTCAE v. 4)
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:The changes in frequency of circulating activated T cells in the skin KS lesions as determined by immunohistochemistry and flow cytometry
Time Frame:6 months
Safety Issue:
Description:
Measure:The changes in number of circulating activated T cells in the skin KS lesions as determined by immunohistochemistry and flow cytometry
Time Frame:6 months
Safety Issue:
Description:
Measure:The changes in frequency of circulating activated T cells in the peripheral blood as determined by flow cytometry
Time Frame:6 months
Safety Issue:
Description:
Measure:The changes in number of circulating activated T cells in the peripheral blood as determined by flow cytometry
Time Frame:6 months
Safety Issue:
Description:
Measure:The changes in PD-1 expression as determined by immunohistochemistry in lesions
Time Frame:6 months
Safety Issue:
Description:
Measure:The changes in PD-L1 expression as determined by immunohistochemistry in lesions
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

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