Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

VA Office of Research and Development

Status and phase: Completed; Phase 2; Phase 1

Conditions: Mouth Neoplasms

Treatments: Drug: Calcitriol; Drug: Celecoxib plus Calcitriol; Drug: Celecoxib

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT00953849

CLIN-003-09S

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 4 patient groups

Arm 1: Celecoxib

Experimental group

Description:

Celecoxib treatment prior to surgery

Treatment:

Drug: Celecoxib

Arm 2: Calcitriol

Experimental group

Description:

Treatment with Calcitriol prior to surgery

Treatment:

Drug: Calcitriol

Arm 3: Celecoxib plus Calcitriol

Experimental group

Description:

Treatment with Celecoxib plus Calcitriol prior to surgery.

Treatment:

Drug: Celecoxib plus Calcitriol

Arm 4: No Treatment

No Intervention group

Description:

no treatment prior to surgery