Clinical Trial: NHS-IL12 for Solid Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: First In-Human Phase I Trial of NHS-IL12 in Patients With Metastatic Solid Tumors

Brief Summary:

Background:

- The experimental drug NHS-IL12 may help the immune system become more active and kill cancer cells that have not responded to standard treatments. NHS-IL12 has been designed to cause less severe side effects than other anticancer drugs, and may be more effective. More research is needed to test NHS-IL12 in people who have solid tumors that have not responded to treatment.

Objectives:

- To test the safety and effectiveness of NHS-IL12 as a treatment for solid tumors which have not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age with solid tumors that have not responded to standard treatments.

Design:

  • Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
  • Participants will receive NHS-IL12 injection every 4 weeks, and will stay in the hospital for at least one day to be monitored with frequent blood tests.
  • Participants will have periodic blood samples taken before treatment and during the first week after treatment for the first two cycles. They will then have blood samples taken before treatment for the rest of the cycles....

Detailed Summary:

Background:

  • Interleukin-12 (IL-12) is a proinflammatory cytokine produced by activated phagocytes and dendritic cells (DCs) that plays a critical role in regulating the transition from innate to adaptive immunity.
  • IL-12 has shown some promising clinical activity in phase I trials, including stabilization of disease in renal cancer patients with partial regression of a metastatic lesion, but has not proceeded further in clinical development due to toxicity.
  • The NHS-IL12 concept is a strategy to reduce the toxicity associated with systemic administration of recombinant human IL-12 by selectively targeting delivery to tumors.

The NHS-IL12 immunocytokine is composed of 2 IL-12 heterodimers, each fused to one of the H-chains of the NHS76 antibody, which has affinity for both single- and double-stranded DNA. Thus, NHS-IL12 targets delivery to regions of tumor necrosis where DNA has become exposed.

Objectives:

  • To determine the dose-limiting toxicities (DLTs) and Maximum Tolerated Dose (MTD) of NHS-IL12 administered subcutaneously every 4 weeks in patients with metastatic or locally advanced solid epithelial or mesenchymal tumors.
  • Secondary objectives include exploring the pharmacokinetics, immunogenicity and immune response of subcutaneously administered NHS-IL12. Based on analysis of immune response, in a preliminary fashion in two expansion cohorts after repeated treatments, the tumor response (irRC) and progression free survival and overall survival will be described.

Eligibility:

  • Exploring the pharmacokinetics, immunogenicity and immune response of subcutaneously administered NHS-IL12. [ Time Frame: 2-3 years ]
  • Describe tumor response (irRC) and progression free survival and overall survival. [ Time Frame: 2-3 years ]


Original Secondary Outcome:

  • Exploring the pharmacokinetics, immunogenicity and immune response of subcutaneously administered NHS-IL12.
  • Describe tumor response (irRC) and progression free survival and overall survival.


Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: August 13, 2011
Date Started: July 29, 2011
Date Completion: January 1, 2020
Last Updated: May 12, 2017
Last Verified: April 7, 2017