Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

January 23, 2017 updated by: VA Office of Research and Development
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29401-5799
        • Ralph H. Johnson VA Medical Center, Charleston, SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: Celecoxib
Celecoxib treatment prior to surgery
Drug: Celecoxib
Celecoxib (400 mg twice daily)
Other Names:
  • 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 Names:
  • 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 Names:
  • 1,25-dihydroxyvitamin D3
No Intervention: Arm 4: No Treatment
no treatment prior to surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in IL-2 Levels
Time Frame: baseline and 3 weeks
Change in IL-2 stimulatory cytokine levels within tumor tissue.
baseline and 3 weeks
Change in IFN-gamma Levels
Time Frame: baseline and 3 weeks
Change in IFN-gamma stimulatory cytokine levels within tumor tissue.
baseline and 3 weeks
Change in GM-CSF
Time Frame: baseline and 3 weeks
Change in GM-CSF stimulatory cytokine levels within tumor tissue.
baseline and 3 weeks
Change in IL-6 Levels.
Time Frame: baseline and 3 weeks
Change in levels of immune inhibitory/inflammatory mediator IL-6 in tumor tissue.
baseline and 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: M. Rita I Young, PhD, Ralph H. Johnson VA Medical Center, Charleston, SC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2009

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

August 4, 2009

First Submitted That Met QC Criteria

August 5, 2009

First Posted (Estimate)

August 6, 2009

Study Record Updates

Last Update Posted (Actual)

March 7, 2017

Last Update Submitted That Met QC Criteria

January 23, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIN-003-09S

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Publication of deidentified results.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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