Celecoxib in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

A Phase I Trial to Evaluate Cyclooxygenase 2 Inhibitor-Mediated Modulation of T Regulatory Cells in Advanced Non-Small Cell Lung Cancer (NSCLC)

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: celecoxib

Detailed Description

OBJECTIVES:

Primary

• Determine the optimal biologic dose (OBD) of celecoxib that is necessary to decrease peripheral blood lymphocyte CD4+ and CD25+ T-lymphocyte regulatory cells in patients with stage IIIB or IV non-small cell lung cancer.

Secondary

• Determine the OBD of this drug that is necessary to decrease peripheral blood lymphocyte FOXP3 levels in these patients.

OUTLINE: This is a nonrandomized, dose-escalation study.

Patients receive oral celecoxib twice daily on days 1-7 in the absence of unacceptable toxicity.

Cohorts of 3 patients receive escalating doses of celecoxib until the optimal biologic dose (OBD) is determined. The OBD is defined as the lowest dose that results in the maximum decrease in peripheral blood lymphocyte CD4+ and CD25+ T-lymphocyte regulatory cells and FOXP3 levels where no dose-limiting toxicity occurs. An additional 15 patients are treated at the OBD.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed non-small cell lung cancer
• Stage IIIB or IV disease
• Radiographically measurable disease
• 18 and over
• Performance status: ECOG 0-2
• Renal: Creatinine ≤ 2 mg/dL
• Negative pregnancy test
• Fertile patients must use effective contraception
• More than 4 weeks since prior chemotherapy
• Endocrine therapy: More than 4 weeks since prior corticosteroids; No concurrent corticosteroids, including chronic corticosteroids, except for medically-indicated topical steroids
• Radiotherapy: More than 4 weeks since prior radiotherapy
• More than 4 weeks since other prior anticancer therapy
• More than 4 weeks since prior non-cytotoxic investigational agents
• At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs)

Exclusion Criteria:

• pregnant or nursing
• comorbid disease, psychiatric condition, chronic medical condition, or laboratory abnormality that would preclude study treatment or compliance with study requirements
• hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or any study reagent
• history of gastrointestinal ulceration, bleeding, or perforation
• other concurrent cyclooxygenase-2 or -3 inhibitors
• other concurrent NSAIDs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: celecoxib	Drug: celecoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Optimal biologic dose (OBD) necessary to decrease peripheral blood lymphocyte (PBL) CD4+ and CD25+ T-lymphocyte regulatory cells at 1 week	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
OBD necessary to decrease PBL FOXP3 levels at 1 week	7 dayd
Function of CD4+ and CD25+ T-regulatory cells at 1 week	7 days
Markers of cyclooxygenase-2 (COX-2) dependent gene expression before and after treatment at 1 week	7 days

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edward Garon, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: March 3, 2005
• First Submitted That Met QC Criteria: March 3, 2005
• First Posted (Estimate): March 4, 2005

Study Record Updates

• Last Update Posted (Estimate): October 2, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: CDR0000415733; UCLA-0407028-01