Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity

• 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: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mouth Neoplasms	Drug: Celecoxib; Drug: Calcitriol; Drug: Celecoxib plus Calcitriol	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Vitamin D Plus Celecoxib Therapy to Stimulate Intratumoral Immune Reactivity
• Study Start Date: November 2009
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• 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

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
• First Posted: August 6, 2009
• Results First Posted: December 21, 2016
• Last Update Posted: March 7, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• 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; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Calcium Channel Agonists; Membrane Transport Modulators