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Vitamin D

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Vitamin D3

Calciferol

Treatment with Calcitriol prior to surgery

Treatment with Celecoxib plus Calcitriol prior to surgery.

3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol 3 for each of 3 sequential days followed by 4 days of no treatment)

3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol for each of 3 sequential days followed by 4 days of no treatment) plus Celecoxib (400 mg twice daily)

Celecoxib plus Calcitriol

M. Rita I Young, PhD

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.

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.

Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Change in IL-2 stimulatory cytokine levels within tumor tissue.

Change in IFN-gamma stimulatory cytokine levels within tumor tissue.

Change in GM-CSF stimulatory cytokine levels within tumor tissue.

Change in levels of immune inhibitory/inflammatory mediator IL-6 in tumor tissue.

VA Office of Research and Development

oral cancer patients receiving Celecoxib prior to surgery

Arm 1: Celecoxib

oral cancer patients receiving Calcitriol prior to surgery

Arm 2: Calcitriol

oral cancer patients receiving Celecoxib + Calcitriol prior to surgery

Arm 3: Celecoxib Plus Calcitriol

oral cancer patients receiving no treatment prior to surgery

Arm 4: No Treatment

Celecoxib:

Celecoxib (400 mg twice daily) oral cancer patients receiving new immunotherapy prior to surgery

Calcitriol Calcitriol (1,25-dihydroxyvitamin D3): 3 week pre-surgical enteral treatment of Calcitriol (3 cycles of 4 microg Calcitriol for each of 3 sequential days followed by 4 days of no treatment)

Celecoxib + Calcitriol 3 week pre-surgical enteral treatment of Calcitriol (3 cycles of 4 microg 1,25-dihydroxyvitamin D3) for each of 3 sequential days followed by 4 days of no treatment) plus Celecoxib (400 mg twice daily)

oral cancer patients receiving no immunotherapy prior to surgery

Total

Age, Categorical

Sex: Female, Male

Difficulty in recruiting subjects that are eligible for the combination Celecoxib + Calcitriol treatment.

M. Rita I. Young, Ph.D.

Celecoxib treatment prior to surgery

Celecoxib: Celecoxib (400 mg twice daily)

Treatment with Calcitriol prior to surgery

Calcitriol: 3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol 3 for each of 3 sequential days followed by 4 days of no treatment)

Treatment with Celecoxib plus Calcitriol prior to surgery.

Celecoxib plus Calcitriol: 3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol for each of 3 sequential days followed by 4 days of no treatment) plus Celecoxib (400 mg twice daily)

Patients with head and neck squamous cell carcinoma.

Change in IL-2 Levels

oral cancer patients receiving new immunotherapy prior to surgery

1,25-dihydroxyvitamin D3: 3 week pre-surgical enteral treatment of 1,25(OH)2D3 (3 cycles of 4 microg 1,25(OH)2D3 for each of 3 sequential days followed by 4 days of no treatment)

oral cancer patients receiving new immunotherapy prior to surgery

celecoxib: celecoxib (400 mg twice daily)

oral cancer patients receiving new immunotherapy prior to surgery

1,25-dihydroxyvitamin D3 + celecoxib: 3 week pre-surgical enteral treatment of 1,25(OH)2D3 (3 cycles of 4 microg 1,25(OH)2D3 for each of 3 sequential days followed by 4 days of no treatment) plus celecoxib (400 mg twice daily)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity	NCT00953849	Mouth Neoplasms	Celecoxib Calcitriol Celecoxib plus ...	18 Years - 85 Years	VA Office of Research and Development
Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity	NCT00953849	Mouth Neoplasms	Celecoxib Calcitriol Celecoxib plus ...	18 Years - 85 Years	VA Office of Research and Development

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