Vitamin D - Celecoxib Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00953849
First received: August 4, 2009
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Mouth Neoplasms
Drug: celecoxib
Drug: 1,25-dihydroxyvitamin D3 + celecoxib
Drug: 1,25-dihydroxyvitamin D3
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Immunological - increased dendritic cell levels, increased T-cell activity [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: November 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
oral cancer patients receiving new immunotherapy prior to surgery
Drug: 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)
Other Name: calcitriol
Experimental: Arm 2
oral cancer patients receiving new immunotherapy prior to surgery
Drug: celecoxib
celecoxib (400 mg twice daily)
Experimental: Arm 3
oral cancer patients receiving new immunotherapy prior to surgery
Drug: 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)
No Intervention: Arm 4
oral cancer patients receiving no immunotherapy prior to surgery

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 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.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953849

Contacts
Contact: Judith Skoner, MD (843) 789-7330 skonerjm@musc.edu

Locations
United States, South Carolina
Ralph H Johnson VA Medical Center, Charleston Recruiting
Charleston, South Carolina, United States, 29401-5799
Contact: Judith Skoner, MD    843-789-7330    skonerjm@musc.edu   
Principal Investigator: M. Rita I Young, PhD         
Sponsors and Collaborators
Investigators
Principal Investigator: M. Rita I Young, PhD Ralph H Johnson VA Medical Center, Charleston
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00953849     History of Changes
Other Study ID Numbers: CLIN-003-09S
Study First Received: August 4, 2009
Last Updated: April 15, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Calcitriol
Celecoxib
Immunotherapy

Additional relevant MeSH terms:
Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Calcitriol
Dihydroxycholecalciferols
Vitamin D
Vitamins
Celecoxib
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014