Vitamin D - Celecoxib Therapy

Mouth Neoplasms Clinical Trial

Official title:

Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00953849
• Other study ID #: CLIN-003-09S
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 4, 2009
• Last updated: January 4, 2016
• Start date: November 2009
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 COX 2 inhibitor celecoxib and/or 1,25(OH)2D3 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 1,25(OH)2D3.

• 2. To reduce development of OSCC recurrences by synergistically stimulating intratumoral T cell reactivity with celecoxib to block suppressor endothelial cell activity and 1,25(OH)2D3 to mature CD34+ suppressor cells into T cell stimulatory dendritic cells.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

• SWOG 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Mouth Neoplasms

Intervention

Drug:
• celecoxib
celecoxib (400 mg twice daily)
• 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)
• 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)

Locations

Country	Name	City	State
United States	Ralph H. Johnson VA Medical Center, Charleston, SC	Charleston	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological - increased dendritic cell levels, increased T-cell activity		3 years	No