Clinical trial NCT00953849: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity
Official title: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mouth Neoplasms
Keywords: Calcitriol
Celecoxib
Immunotherapy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2009-08-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in IL-2 Levels
timeFrame: baseline and 3 weeks
measure: Change in IFN-gamma Levels
timeFrame: baseline and 3 weeks
measure: Change in GM-CSF
timeFrame: baseline and 3 weeks
measure: Change in IL-6 Levels.
timeFrame: baseline and 3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC
name: M. Rita I Young, PhD
role: PRINCIPAL_INVESTIGATOR
References: