Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Phase 1

Completed

• Conditions: Mouth Neoplasms
• Interventions: Drug: Celecoxib; Drug: Celecoxib plus Calcitriol; Drug: Calcitriol

• Registration Number: NCT00953849
• Lead Sponsor: VA Office of Research and Development

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 Description

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.

Study Timeline

• Study First Submitted: 2009-08-04
• Study First Submitted QC: 2009-08-05
• Study First Posted: 2009-08-06
• Study Start: 2009-11
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Results First Submitted: 2016-09-06
• Results First Submitted QC: 2016-10-27
• Results First Posted: 2016-12-21
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-23
• Last Update Posted: 2017-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Celecoxib	Celecoxib	Celecoxib treatment prior to surgery
Arm 3: Celecoxib plus Calcitriol	Celecoxib plus Calcitriol	Treatment with Celecoxib plus Calcitriol prior to surgery.
Arm 2: Calcitriol	Calcitriol	Treatment with Calcitriol prior to surgery

Primary Outcome Measures

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

Trial Locations

Locations (1)

Ralph H. Johnson VA Medical Center, Charleston, SC; 🇺🇸 Charleston, South Carolina, United States