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Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00953849
First received: August 4, 2009
Last updated: October 27, 2016
Last verified: October 2016
  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: Calcitriol
Drug: Celecoxib plus Calcitriol
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
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 VA Office of Research and Development:

Primary Outcome Measures:
  • Change in IL-2 Levels [ Time Frame: baseline and 3 weeks ]
    Change in IL-2 stimulatory cytokine levels within tumor tissue.

  • Change in IFN-gamma Levels [ Time Frame: baseline and 3 weeks ]
    Change in IFN-gamma stimulatory cytokine levels within tumor tissue.

  • Change in GM-CSF [ Time Frame: baseline and 3 weeks ]
    Change in GM-CSF stimulatory cytokine levels within tumor tissue.

  • Change in IL-6 Levels. [ Time Frame: baseline and 3 weeks ]
    Change in levels of immune inhibitory/inflammatory mediator IL-6 in tumor tissue.


Enrollment: 21
Study Start Date: November 2009
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Celecoxib
Celecoxib treatment prior to surgery
Drug: Celecoxib
Celecoxib (400 mg twice daily)
Other Name: Celebrex
Experimental: Arm 2: Calcitriol
Treatment with Calcitriol prior to surgery
Drug: Calcitriol
3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol 3 for each of 3 sequential days followed by 4 days of no treatment)
Other Name: 1,25-dihydroxyvitamin D3
Experimental: Arm 3: Celecoxib plus Calcitriol
Treatment with Celecoxib plus Calcitriol prior to surgery.
Drug: Celecoxib plus Calcitriol
3 week pre-surgical enteral treatment of Calcitriol (1,25-dihydroxyvitamin D3) (3 cycles of 4 microg Calcitriol for each of 3 sequential days followed by 4 days of no treatment) plus Celecoxib (400 mg twice daily)
Other Name: 1,25-dihydroxyvitamin D3
No Intervention: Arm 4: No Treatment
no treatment 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 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

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • 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

Locations
United States, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, United States, 29401-5799
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: M. Rita I Young, PhD Ralph H. Johnson VA Medical Center, Charleston, SC
  More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00953849     History of Changes
Other Study ID Numbers: CLIN-003-09S 
Study First Received: August 4, 2009
Results First Received: September 6, 2016
Last Updated: October 27, 2016
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Publication of deidentified results.

Keywords provided by VA Office of Research and Development:
Calcitriol
Celecoxib
Immunotherapy

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

ClinicalTrials.gov processed this record on February 17, 2017