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Summary

for people ages 18 years and up (full criteria)
study started
estimated completion:

Description

Summary

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.

Official Title

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

Details

Infection with Kaposi sarcoma herpesvirus (KSHV, or human herpesvirus-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/PD-L1 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.

Keywords

Kaposi Sarcoma HIV/AIDS Immunosuppression Sarcoma Sarcoma, Kaposi Skin Neoplasms Nivolumab Antibodies, Monoclonal

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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
  • ECOG performance status of 0 or 1

You CAN'T join if...

  • 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.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03316274
Phase
Phase 1
Lead Scientist
Chia-ching Wang
Study Type
Interventional
Last Updated
October 16, 2017
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