Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

November 14, 2015 updated by: Radiation Therapy Oncology Group

A Phase I/II Trial of a COX-2 Inhibitor, Celebrex (Celecoxib), [National Screening Committee# 719627] With Limited Field Radiation for Intermediate Prognosis Patients With Locally Advanced Non-Small Cell Lung Cancer, With Analysis of Prognostic Factors

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Celecoxib may stop the growth of tumor cells by stopping blood flow to the tumor and may make the tumor cells more sensitive to radiation therapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining celecoxib with radiation therapy in treating patients who have locally advanced non-small cell lung cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose and the recommended phase II dose of concurrent celecoxib and limited-field radiotherapy in intermediate-prognosis patients with locally advanced non-small cell lung cancer.
  • Determine the efficacy and toxicity of this regimen in these patients.
  • Determine how the predictors of mortality in the general population (i.e., comorbid conditions, functional status, quality of life, and psychological status) influence prognosis, toxicity, and outcomes of therapy in patients treated with this regimen.
  • Correlate circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL8) with survival in patients treated with this regimen.
  • Correlate circulating levels of interleukin-1 (IL1), interleukin-6 (IL6), and transforming growth factor-beta (TGFB) with pulmonary toxicity in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of celecoxib followed by a phase II, multicenter study.

  • Phase I: Patients receive oral celecoxib twice daily. Beginning on day 6, patients undergo thoracic radiotherapy 5 days a week for 3-6.5 weeks . Patients continue to receive celecoxib for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Phase II: If fewer than 3 of the first 6 patients experience dose-limiting toxicity, then the dose of celecoxib is escalated for all patients in the study, including those in the first cohort.

Quality of life is assessed at baseline and at 3, 6, and 12 months after start of therapy.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-12 patients will be accrued for the phase I portion of this study and a total of 116 patients will be accrued for the phase II portion of this study within 25 months.

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
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Memorial Hospital Cancer Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Shands Cancer Center
      • Jacksonville, Florida, United States, 32207
        • Baptist Cancer Institute - Jacksonville
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center
    • Georgia
      • Rome, Georgia, United States, 30165
        • Regional Radiation Oncology Center at Rome
    • Illinois
      • Harvey, Illinois, United States, 60426
        • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Cancer Center
    • Iowa
      • Dubuque, Iowa, United States, 52001
        • Wendt Regional Cancer Center at Finley Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55403
        • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
      • Saint Louis Park, Minnesota, United States, 55416
        • CCOP - Metro-Minnesota
      • St. Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • CCOP - Kansas City
      • Springfield, Missouri, United States, 65804
        • St. John's Regional Health Center
    • New Jersey
      • Long Branch, New Jersey, United States, 07740
        • Monmouth Medical Center
      • Mount Holly, New Jersey, United States, 08060
        • Fox Chase Virtua Health Cancer Program - Marlton
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Albuquerque Regional Medical Center at Lovelace Sandia Health System
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Research and Treatment Center
    • North Dakota
      • Minot, North Dakota, United States, 58701
        • Trinity Cancer Care Center
    • Ohio
      • Akron, Ohio, United States, 44304
        • Akron City Hospital at Summa Health System
      • Alliance, Ohio, United States, 44601
        • Radiation Oncology Center
      • Salem, Ohio, United States, 44460
        • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
      • Wooster, Ohio, United States, 44691
        • Cancer Treatment Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at St. Francis Hospital
    • Pennsylvania
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Bryn Mawr Hospital
      • Paoli, Pennsylvania, United States, 19301
        • Cancer Center at Paoli Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center
      • Scranton, Pennsylvania, United States, 18501
        • Mercy Hospital Cancer Center - Scranton
      • Wynnewood, Pennsylvania, United States, 19096
        • CCOP - MainLine Health
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Cancer Center at Lankenau Hospital
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • CCOP - Greenville
      • Spartanburg, South Carolina, United States, 29304
        • CCOP - Upstate Carolina
    • Utah
      • Provo, Utah, United States, 84603
        • Utah Valley Regional Medical Center - Provo
      • Salt Lake City, Utah, United States, 84143
        • LDS Hospital
      • St. George, Utah, United States, 84770
        • Dixie Regional Medical Center
    • Washington
      • Bellingham, Washington, United States, 98225
        • St. Joseph Hospital Community Cancer Center
      • Yakima, Washington, United States, 98902
        • North Star Lodge Cancer Center
    • Wisconsin
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
      • Menomonee Falls, Wisconsin, United States, 53051
        • Community Memorial Hospital
      • Milwaukee, Wisconsin, United States, 53295
        • Veterans Affairs Medical Center - Milwaukee (Zablocki)
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin Cancer Center
      • Racine, Wisconsin, United States, 53405
        • All Saints Cancer Center at All Saints Healthcare
      • Wausau, Wisconsin, United States, 54401
        • University of Wisconsin Cancer Center at Aspirus Wausau Hospital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer

    • Inoperable stage IIB OR
    • Unresectable stage IIIA or IIIB
    • No evidence of hematogenous metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 2 AND more than 5% weight loss over the past 3 months OR
  • Zubrod 0-1 AND less than 5% weight loss over the past 3 months and refuses chemotherapy or are medically unable to tolerate combined modality therapy

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin no greater than 2 times upper limit of normal
  • International Normalized Ratio (INR) no greater than 3.0 if taking warfarin

Renal

  • Creatinine clearance at least 50 mL/min

Other

  • No active gastrointestinal ulcers or bleeding within the past 3 months
  • No other malignancy within the past 3 years except nonmelanoma skin cancer
  • No known hypersensitivity to celecoxib
  • No prior allergic-type reactions to sulfonamides
  • No prior asthma, urticaria, or allergic-type reactions to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior neoadjuvant chemotherapy
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent corticosteroids

Radiotherapy

  • No prior thoracic radiotherapy

Surgery

  • No prior complete or subtotal tumor resection

Other

  • No concurrent NSAIDs, lithium, furosemide, or angiotensin-converting enzyme inhibitors
  • Concurrent aspirin (325 mg/day) for cardioprotection allowed

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I: Celecoxib 200mg BID + RT

COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Radiation: radiation therapy
Drug: celecoxib
Other Names:
  • COX-2 Inhibitor
Experimental: Phase I: Celecoxib 400mg BID + RT

COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Radiation: radiation therapy
Drug: celecoxib
Other Names:
  • COX-2 Inhibitor
Experimental: Phase II: Celecoxib 400mg BID + RT

COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Radiation: radiation therapy
Drug: celecoxib
Other Names:
  • COX-2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT)
Time Frame: Start of treatment to 90 days

Patients were followed for at least 90 days from start of RT and carefully evaluated with respect to treatment morbidity. A dose limiting toxicity (DLT) was defined as grade 3 or 4 nonhematologic (excluding nausea, vomiting, and alopecia) and grade 4 hematologic toxicities. Six patients were to be accrued at each dose level. If no more than three of the six patients experienced a DLT then that dose level was considered acceptable and dose escalation occurred by accruing six more patients at the next dose level. Otherwise, the preceding dose level, if any, would be declared the MTD. The MTD would be used for the Phase II arm. At a given dose, the probability of halting dose escalation when the true toxicity is 50% or higher is at least 66% (power). In addition, if the true DLT rate is instead 20%, there will still be a 10% probability of halting dose escalation at a given dose level (type I error).

Rating scale: 0 = not the MTD, 1 = MTD
Start of treatment to 90 days
Overall Survival
Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months.
Because only 21 patients (18 analyzable) out of 128 planned were accrued on this study, all analyzable patients were combined to report overall survival. The original study design planned for a comparison to a historical control, but due to the small number of patients, survival time is only reported, not tested.
From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months.

Collaborators and Investigators

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

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Elizabeth M. Gore, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2002

Primary Completion (Actual)

September 1, 2011

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

October 3, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

November 17, 2015

Last Update Submitted That Met QC Criteria

November 14, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTOG-0213
  • CDR0000069476

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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