Clinical Trial: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Brief Summary: The poor survival of Veterans with oral cancer underscores the significance of identifying new treatment approaches. The proposed studies will test a new 2 pronged immunotherapeutic approach for oral cancer patients which lessen the immune inhibitory environment while maturing cells that can stimulate T cell reactivity against oral cancer cells.

Detailed Summary:

The hypothesis of this study is beneficial T cell reactivity in oral squamous cell carcinoma (OSCC) tumors can be synergistically stimulated by blocking suppressor endothelial cells and their induction of other inhibitory cell populations while also maturing immune inhibitory CD34+ cells into antigen-presenting dendritic cells.

To test this hypothesis, newly diagnosed OSCC patients will be administered the cyclooxigenase 2 inhibitor celecoxib and/or Calcitriol for the 3 week duration between cancer diagnosis and surgical treatment. The following aims will test the immunological and clinical effectiveness of the combination treatment:

• 1. To block the suppressive activity of endothelial cells and increase the levels of dendritic that are stimulatory to T cell reactivity, thereby synergistically increasing intratumoral T cell reactivity. These functional immune analyses will use OSCC tissues removed from untreated patients or patients treated with celecoxib and/or Calcitriol.
• 2. To reduce development of OSCC recurrences by synergistically stimulating intratumoral T cell reactivity with celecoxib to block suppressor endothelial cell activity and Calcitriol to mature CD34+ suppressor cells into T cell stimulatory dendritic cells.

Sponsor: VA Office of Research and Development

Current Primary Outcome:

• Change in IL-2 Levels [ Time Frame: baseline and 3 weeks ]
  Change in IL-2 stimulatory cytokine levels within tumor tissue.
• Change in IFN-gamma Levels [ Time Frame: baseline and 3 weeks ]
  Change in IFN-gamma stimulatory cytokine levels within tumor tissue.
• Change in GM-CSF [ Time Frame: baseline and 3 weeks ]
  Change in GM-CSF stimulatory cytokine levels within tumor tissue.
• Change in IL-6 Levels. [ Time Frame: baseline and 3 weeks ]
  Change in levels of immune inhibitory/inflammatory mediator IL-6 in tumor tissue.

Original Primary Outcome: Immunological - increased dendritic cell levels, increased T-cell activity [ Time Frame: 5 years ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: VA Office of Research and Development

Dates:
Date Received: August 4, 2009
Date Started: November 2009
Date Completion:
Last Updated: January 23, 2017
Last Verified: January 2017