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Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00953849
Recruitment Status : Completed
First Posted : August 6, 2009
Results First Posted : December 21, 2016
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE August 4, 2009
First Posted Date  ICMJE August 6, 2009
Results First Submitted Date  ICMJE September 6, 2016
Results First Posted Date  ICMJE December 21, 2016
Last Update Posted Date March 7, 2017
Study Start Date  ICMJE November 2009
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2016)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 5, 2009)
Immunological - increased dendritic cell levels, increased T-cell activity [ Time Frame: 5 years ]
Change History Complete list of historical versions of study NCT00953849 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity
Official Title  ICMJE Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Mouth Neoplasms
Intervention  ICMJE
  • Drug: Celecoxib
    Celecoxib (400 mg twice daily)
    Other Name: Celebrex
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Arm 1: Celecoxib
    Celecoxib treatment prior to surgery
    Intervention: Drug: Celecoxib
  • Experimental: Arm 2: Calcitriol
    Treatment with Calcitriol prior to surgery
    Intervention: Drug: Calcitriol
  • Experimental: Arm 3: Celecoxib plus Calcitriol
    Treatment with Celecoxib plus Calcitriol prior to surgery.
    Intervention: Drug: Celecoxib plus Calcitriol
  • No Intervention: Arm 4: No Treatment
    no treatment prior to surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 27, 2016)
21
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2009)
140
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00953849
Other Study ID Numbers  ICMJE CLIN-003-09S
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Publication of deidentified results.
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: M. Rita I Young, PhD Ralph H. Johnson VA Medical Center, Charleston, SC
PRS Account VA Office of Research and Development
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP