Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Study Overview
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Brief Summary
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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 Description
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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.

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

Conditions
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Mouth Neoplasms

Intervention / Treatment
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* Drug: Celecoxib
* Drug: Calcitriol
* Drug: Celecoxib plus Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: locoregional OSCC (T stage II-IV) of the oral cavity, oropharynx, larynx, or hypopharynx without evidence of distant metastases greater than or equal to 18 years of age the OSCC treatment plan includes surgical resection performance status of 0 or 1 recovered from any prior surgery must be willing to use appropriate contraception if of child-bearing potential give signed informed consent prior to the initiation of therapy Exclusion Criteria: prior immunotherapy chemotherapy or radiation therapy within three weeks concurrent NSAID treatments while undergoing treatment women pregnant or lactating HIV positive have an active infection requiring antibiotic therapy, or concomitant malignancies history of idiopathic urinary calcium stone disease, chronic hypercalcemia, or gastrointestinal malabsorptive conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Celecoxib<br>Celecoxib treatment prior to surgery | Drug: Celecoxib<br>* Celecoxib (400 mg twice daily)<br>* Other names: Celebrex;|
| Experimental: Arm 2: Calcitriol<br>Treatment with Calcitriol prior to surgery | Drug: Calcitriol<br>* 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)<br>* Other names: 1,25-dihydroxyvitamin D3;|
| Experimental: Arm 3: Celecoxib plus Calcitriol<br>Treatment with Celecoxib plus Calcitriol prior to surgery. | Drug: Celecoxib plus Calcitriol<br>* 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)<br>* Other names: 1,25-dihydroxyvitamin D3;|
| No Intervention: Arm 4: No Treatment<br>no treatment prior to surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-2 Levels | Change in IL-2 stimulatory cytokine levels within tumor tissue. | baseline and 3 weeks | 
| Change in IFN-gamma Levels | Change in IFN-gamma stimulatory cytokine levels within tumor tissue. | baseline and 3 weeks | 
| Change in GM-CSF | Change in GM-CSF stimulatory cytokine levels within tumor tissue. | baseline and 3 weeks | 
| Change in IL-6 Levels. | Change in levels of immune inhibitory/inflammatory mediator IL-6 in tumor tissue. | baseline and 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcitriol, Celecoxib, Immunotherapy